What changed in this filing

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Item 1. Business

2023-03-02 compared with 2022-03-28 · 241 added, 222 removed, 109 unchanged (81% of the section changed)

Medical Corporation is a med-tech company focused on improving the standard of care in the treatment of venous disease.

We are developing

tissue-based solutions that are designed to be life sustaining or life enhancing for patients with Chronic Venous Insufficiency (CVI).

CVI occurs when valves inside of the veins of the leg fail, resulting in insufficient blood being returned to the heart.

develop products to address large unmet medical needs by either offering treatments where none currently exist or by substantially

increasing the current standards of care.

Our lead product is a porcine based device to be surgically implanted in the deep venous system

of the leg and is called the VenoValve®.

The VenoValve is currently being evaluated in the SAVVE U.S.

pivotal trial for the

purpose of obtaining approval to market and sell the device from the U.S.

Medical Corporation is a late stage clinical med-tech company focused on the advancement of innovative bioprosthetic

(tissue-based) solutions to improve the standard of care for the treatment of venous disease.

Chronic Venous Disease (CVD) is the

world’s most prevalent chronic disease, impacting approximately 71% of the adult population of the U.S.

Chronic Venous

Insufficiency (CVI), is a large subset of CVD, which most often occurs when valves inside of the veins of the leg become damaged,

resulting in the backwards flow of blood (reflux), blood pooling in the lower leg, increased pressure in the veins of the leg

(venous hypertension) and in severe cases, venous ulcers that are difficult to heal.

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.

Company’s lead product is the VenoValve®, which is a first-in-class surgical replacement venous valve that is currently 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 currently waiting for regulatory approval to begin a first-in-human study

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.

VenoValve and enVVe are being developed first for approval by the U.S.

Food and Drug Administration (FDA).

of officers and directors has been affiliated with numerous medical devices that have received FDA approval or CE marking and that have

been commercially successful.

We expect the VenoValve to

be eligible for FDA approval first, followed two to three years later by enVVe.

Once approved, we expect 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.

currently 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.

team of officers and directors has been affiliated with numerous medical devices that have received FDA approval or CE marking and that

have been commercially successful.

We develop and manufacture our products in a 14,507 sq.

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.

September 21, 2021, we announced that we were changing our name from Hancock Jaffe Laboratories, Inc.

to enVVeno Medical Corporation

and that our development strategy is to focus on the treatment of deep venous CVI.

In addition to the VenoValve, we announced

that we have a second product in the early stages of development called enVVe.

In connection with this change in strategy, we indicated

that we are not pursuing further development of the CoreoGraft, which is now outside of our primary focus area.

VenoValve is a porcine based valve developed at enVVeno Medical to be implanted in the deep venous system of the leg to treat severe

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 current version of the VenoValve is designed to be implanted into the femoral vein of the patient in an open surgical procedure via

a 5-to-6-inch incision in the upper thigh.

are presently no FDA approved medical devices to address valvular incompetence in the deep venous system, or effective treatments for

deep venous CVI.

Current treatment options include compression garments, or constant leg elevation, and would care for venous ulcers.

These treatments are generally ineffective, as they attempt to alleviate the symptoms of CVI without addressing the underlying causes

of the disease.

In addition, we believe compliance with compression garments and leg elevation is extremely low, especially among the

The premise behind the VenoValve is that by reducing the underlying causes of CVI, reflux and venous hypertension, the debilitating

symptoms of CVI will decrease, resulting in improvement in the quality of the lives of CVI sufferers.

estimate that there are approximately 2.4 million people in the U.S.

that suffer from deep venous CVI due to valvular incompetence.

venous disease (“CVD”) is the world’s most prevalent chronic disease.

CVD is generally 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 C5 to C6 being the most severe cases of CVD.

Venous Insufficiency (“CVI”) is a 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).

leased manufacturing facility in Irvine,

California, which has been ISO 13485-2020 certified for the design, development and manufacturing of tissue based implantable medical

CVI Background

Chronic venous disease (“CVD”)

is the world’s most prevalent chronic disease.

CVD is generally 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

the deep vein system, the superficial vein system, and the perforator vein system which connects the deep system to the superficial

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.

The VenoValve is being developed to treat CVI in the deep venous system with a focus on severe patients with C4b, C5 and C6 CVI.

estimate that approximately 2.4 million people in the U.S.

have C5 to C6 CVI due to reflux in the deep venous system, including patients

that develop venous leg ulcers (C6 patients).

Over one million new severe cases of CVI occur each year in the U.S., mostly from patients

who have experienced a deep vein thrombosis or blood clot.

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

$38 billion a year.

Aside from the direct medical costs, severe CVI sufferers experience a significantly reduced quality of life.

activities such as preparing meals, housework, and personal hygiene (washing and bathing) become difficult due to reduced mobility.

many severe CVI sufferers, intense pain, which frequently occurs at night, prevents patients from getting adequate sleep.

sufferers are known to miss approximately 40% more work days 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

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.

Reflux, and the resulting

venous hypertension, causes the leg to swell, resulting in debilitating pain, and in the most severe cases, venous ulcers.

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 patients

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.

Prevalence is generally defined

as the portion of the population that has a given condition.

Estimates indicate that the prevalence of people in the U.S.

deep venous CVI (C4 to C6 disease) with reflux to be approximately 20 million.

Incidence is generally defined as the number of new cases

of an ailment that develop in a given time period.

We estimate that approximately 3.5 million new patients with severe deep venous CVI

are diagnosed each year in the U.S.

including 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

has been estimated to exceed $3 billion a year.

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

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

As our planned initial entrant to the replacement venous valve market, we estimate that approximately 2.5 million people

with severe deep venous CVI in the U.S.

would be candidates for the VenoValve.

Clinical Status

consultation with the FDA, and as a precursor to the U.S.

pivotal trial, we 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 valuable feedback to make any necessary product modifications or adjustments to

our surgical implantation procedure for the VenoValve prior to conducting the U.S.

pivotal trial, in 2020 we 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 our 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 doppler, a VCSS score used by the clinician to measure disease

severity and progress, a VAS score used by the patient to measure pain, and a quality of life measurement.

results from the one (1) year first-in-human study were presented at the Charing Cross International Symposium in April of 2021.

the eleven (11) patients in the study, reflux improved an average of 54%, Venous Clinical Severity Scores (“VCSSs”) improved

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.

from the one year first-in-human study were presented at the Charing Cross International Symposium in April of 2021.

eleven (11) patients in the study, reflux improved an average of 54%, Venous Clinical Severity Scores (“VCSSs”) improved

an average of 56%, and visual analog scale (VAS) scores, which are used by patients to measure pain, improved an average of 76%, all

at one (1) year when compared to pre-surgery levels.

VCSS scores are commonly used by clinicians in practice and in clinical trials to

objectively assess outcomes in the treatment of venous disease, and include ten characteristics including pain, inflammation, skin changes

such as pigmentation and induration, the number of active ulcers, and ulcer duration.

The improvement in VCSS scores is significant and

indicates the VenoValve patients who had severe CVI pre-surgery, had mild CVI or the complete absence of disease at one-year post surgery.

were no device related safety incidences during the one (1) year first-in-human study.

Non-device related safety incidences were minor

and 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.

preparation for the VenoValve U.S.

pivotal trial, on March 5, 2021, we submitted an IDE application with the FDA.

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.

On April 1, 2021, we received notification from the FDA that our IDE application was approved.

We have named

pivotal trial for the VenoValve the SAVVE (Surgical Anti-reflux Veno Valve Endoprosthesis) study.

It is a prospective,

non-blinded, single arm, multi-center study of seventy-five (75) CVI patients to be enrolled at up to 20 U.S.

modifications for the VenoValve were necessary following the first-in-human study and the SAVVE trial is evaluating the same device that

was used in the first-in-human study.

Endpoints for the SAVVE trial mirror those endpoints used for the first-in-human study.

The primary safety endpoint for the pivotal trial is a material adverse safety event (mortality, deep wound infection, major bleeding,

ipsilateral deep vein thrombosis, pulmonary embolism) in no more than twenty six percent (26%) of the patients at one (1) month

post implantation, and the primary effectiveness endpoint for the pivotal trial is improvement in reflux of at least thirty percent (30%),

measured at six (6) months post VenoValve implantation.

In the first-in-human study there were no reported material adverse safety events

at one (1) month post implantation, and reflux improved an average of fifty six percent (56%) at six (6) months post implantation.

scoring to measure disease manifestations, VAS scores to measure pain, and quality of life measurements will also be monitored in the

August 3, 2020, we 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.

the end of the VenoValve first-in-human study, eight (8) study participants agreed to additional monitoring.

In August of 2021, longer

term follow-up data was presented at the Society of Vascular Surgery Conference in San Diego, for the cohort of eight (8) patients.

data indicated no recurrences of the severe CVI that was present pre-VenoValve, including no ulcer recurrences for those patients whose

venous ulcers had healed following VenoValve surgery.

There were no reported safety issues from the end of one (1) year first-in-human

study to the end of the two (2) year reporting period.

In addition, the patients continued to improve, reporting 63%, 60%, and 93%, average

improvements in reflux, VCSS, and VAS scores, respectively, at an average of two (2) years post VenoValve surgery compared to pre-VenoValve

October of 2021, we announced that the first patient in the SAVVE pivotal trial underwent successful VenoValve implantation surgery

and had been discharged from the hospital.

The surgery was performed by Dr.

Adriana Laser, associate professor of surgery at Albany

Medical College and a vascular surgeon with Albany Med Vascular Surgery.

As of December 31, 2021, ten (10) of our clinical trial

sites were activated and eligible to enroll patients in the SAVVE pivotal trial.

As of March 24, 2022 we have sixteen (16)

clinical trial sites that are active to enroll patients in the SAVVE trial and expect to have nineteen (19) active sites by March

Also, as of March 24, 2022, we have completed nine (9) successful surgeries in the SAVVE pivotal trial for the VenoValve.

We expect to have our tenth surgery completed by March 31, 2022.

resurgence of COVID and the Omicron variant had both direct and indirect consequences on our clinical trial.

Several of our clinical

sites put elective surgeries on hold and prohibited potential study subjects from coming to the hospital for screening.

Further, as reported

in the media, COVID resurgences put an enormous strain on all hospital resources including clinical staffs.

In addition to caring for

the influx of COVID patients, hospitals become short staffed due to their own employees’ COVID sicknesses, resulting in clinical

staff being reassigned to cover the shortfall.

The lack of available clinical personnel both slows enrollment and impacts the speed at

which we can activate clinical sites.

COVID impacts our patient population.

Patients with COVID or who have had COVID within ninety (90) days of their screening, are excluded

from our study until after the ninety (90) day period has passed.

In addition, concerns about getting COVID impact the patients’

willingness to undergo an elective surgical procedure with a one-night hospital stay.

As hospital clinical operations return to more

normal levels, our goal is to fully enroll the SAVVE pivotal trial by the end of 2022 or the beginning of 2023.

continue to monitor the ongoing overall impact of COVID on the SAVVE clinical trial and will issue updates when appropriate.

February of 2021, we raised $41.4 million of capital in a public offering of our common stock.

In September of 2021, we raised

$20 million dollars of capital in a registered direct offering priced at the market under Nasdaq rules and purchased by a fund

managed by Perceptive Advisors, a leading life sciences investment firm.

We finished 2021 with approximately $55 million of cash.

At our existing cash burn rate of approximately $4 million per quarter, we should have sufficient cash to fund operations through the

end of 2024 and into 2025.

With primary endpoints following full enrollment in the SAVVE pivotal trial of thirty (30) days for safety,

and six (6) months for effectiveness, we expect to have primary endpoint data well in advance of the need to raise additional capital.

VCSS scores are commonly used by clinicians in practice and in clinical trials

to objectively assess outcomes in the treatment of venous disease, and include ten characteristics including pain, inflammation,

skin changes such as pigmentation and induration, the number of active ulcers, and ulcer duration.

The improvement in VCSS scores is

significant and indicates the VenoValve patients who had severe CVI pre-surgery, had mild CVI or the complete absence of disease at

one-year post surgery.

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

On August 3, 2020, we 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, we submitted an

IDE application with the FDA and in April 2021, we received notification from the FDA that our 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

This approval allowed us to proceed with our 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.

We 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.

November of 2022, we announced we had passed a preliminary safety review by the FDA for the first twenty (20) patients enrolled in the

The FDA had requested that we submit 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.

continue to be severely understaffed, which impacts the rate at which clinical trials enroll and progress.

We have taken several steps

to help address the hospital staffing shortages, including our 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 the date of this Annual Report,

we have twenty (20) clinical trial sites activated and eligible to enroll patients in the SAVVE trial and have completed forty-three

(43) successful surgeries.

Our guidance is to reach full enrollment in the SAVVE study by the end of the second quarter of 2023.

Enrollment continues to be somewhat inconsistent, with strong enrollment months interspersed with slower enrollment months.

change the guidance, if necessary, if and when we determine that new guidance is necessary.

On September 21, 2022, we 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 our announcement.

We also filed an application

seeking approval to begin first-in-human (FIH) testing in Columbia which we expect 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, we expect 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.

Cash Position

During 2021 we raised $61.4 million

in gross proceeds from capital in offerings of our securities including a public offering in February, and a registered direct offering

in September priced at the market under Nasdaq rules and purchased by a fund managed by Perceptive Advisors, a leading life sciences investment

We finished 2022 with approximately $39.1 million of cash and investments.

At our existing cash burn rate of approximately $4 to

$5 million per quarter, we should have sufficient cash to fund operations through the end of 2024 and into 2025.

product candidates and our operations are subject to extensive regulation by the FDA, and other federal and state authorities in the

7 unchanged sentences

Approval Pathway

III devices such as the VenoValve 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.

In a PMA, the manufacturer must demonstrate that

the device is safe and effective, and the PMA must be supported by extensive data, including data from preclinical studies and human

clinical trials.

The PMA also must contain a full description of the device and its components, a full description of the methods, facilities

and controls used for manufacturing, and proposed labeling.

Following receipt of a PMA, the FDA determines whether the application is

sufficiently complete to permit a substantive review.

If FDA accepts the application for review, it has 180 days under the FDCA to complete

its review of a PMA, although in practice, the FDA’s review often takes significantly longer, and can take several years.

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 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).

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

PMA review and approval process is more demanding than the 510(k) premarket notification process.

In a PMA, the manufacturer must

demonstrate that the device is safe and effective, and the PMA must be supported by extensive data, including data from preclinical

studies and human clinical trials.

The PMA also must contain a full description of the device and its components, a full description

of the methods, facilities and controls used for manufacturing, and proposed labeling.

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, although in practice, the FDA’s review often takes

significantly longer, and can take several years.

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 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).

FDA may approve a PMA with post-approval conditions intended to ensure the safety and effectiveness of the device, including, among other

6 unchanged sentences

certain patient groups for a number of years and to make periodic reports to the FDA on the clinical status of those patients.

to comply with the conditions of approval can result in material adverse enforcement action, including withdrawal of the approval.

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.

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 extensive 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

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 extensive 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.

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disease or otherwise preventing impairment of human health, or otherwise presents a potential for serious risk to a subject.

VenoValve required IDE applications prior to human testing in the United States, and we believe any future products such as

the enVVE will also require IDE applications before human testing in the United States.

The VenoValve

required IDE applications prior to human testing in the United States, and we believe any future products such as the enVVe will also

require IDE applications before human testing in the United States.

IDE application must be supported by appropriate data, such as animal and laboratory test results, showing that it is safe to test the

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or other concerns with an IDE for which it requires modification, the FDA may permit a clinical trial to proceed under a conditional

addition to IDE approval, a human, the study must be approved by, and conducted under the oversight of, an Institutional Review Board,

or IRB, for each clinical site.

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

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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.

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

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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.

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.

Competitive Strengths

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:

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:

have extensive experience of proprietary processing and manufacturing methodology specifically applicable to the design, processing,

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tissue preservation and gamma irradiation that enhances device functions and guarantees sterility.

We have filed several patent applications

We have filed numerous patent applications

for the VenoValve with the U.S.

Patent and Trademark Office (USPTO) and throughout the world.

In February of 2021, we

received a notice for allowance from the USPTO for an application focusing on novel aspects of the VenoValve Frame.

of March 24, 2022, we had 24 full-time employees.

None of our employees are represented by a collective bargaining agreement,

and we have never experienced any work stoppage.

We currently have seventeen (17) patents

granted from agencies around the world including four (4) from the USPTO.

of February 27, 2023, we had thirty (30) 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.

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The information contained on or accessible

through our website is not a part of this prospectus, and the inclusion of our website address in this prospectus is an inactive textual

reference only.

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.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business