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Item 1. Business

2024-02-29 compared with 2023-03-02 · 220 added, 234 removed, 116 unchanged (80% of the section changed)

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.

Medical Corporation is a late clinical-stage medical device 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 70% 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

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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.

The Company is currently conducting pre-clinical testing on 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.

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

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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 13485-2020 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).

If 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, although

we cannot provide any assurance that either the VenoValve or 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.

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 connection with our clinical trials in a 14,507

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.

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.

Venous Insufficiency (“CVI”) is a large subset of CVD and is generally used to describe patients with C4 to C6 CVD.

a debilitating condition that affects the venous system of the leg causing pain, swelling, edema, skin changes, and ulcerations.

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.

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.

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

venous ulcers.

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.

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.

is generally defined as the portion of the population that has a given condition.

Estimates indicate that the prevalence of people in

with severe, 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

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 $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.

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 caused by valvular incompetence.

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 our planned initial entrant to

the replacement venous valve market, we estimate that approximately 2.5 million people each year with severe deep venous CVI in the

would be candidates for the VenoValve.

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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 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.

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 VenoValve pivotal trial.

Endpoints for the VenoValve first-in-human study included safety (device

related adverse events), popliteal reflux time, measured by Duplex Ultrasound, rVCSS scoring, which is a measurement created by

international vascular societies and is used by the clinician to measure disease progression and regression, 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.

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.

eleven (11) patients in the study, rVCSS scores improved an average of 6 points, popliteal reflux time improved an average of 54%,

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.

Revised Venous Clinical Severity Scoring (rVCSS) is a validated measurement commonly used to

objectively assess outcomes in the treatment of venous disease, and include ten characteristics consisting of physician assessments

and patient reported outcomes including pain, inflammation, skin changes such as pigmentation and induration, the number of active

ulcers, and ulcer duration.

The improvement in VCSS scores was 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.

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.

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

In November of 2022, three-year, positive

follow-up data was presented for this cohort of patients at the 49th Annual VEITH Symposium in New York city.

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.

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 device.

This approval allowed us to proceed with our U.S.

pivotal study for the VenoValve which

is called the SAVVE (Surgical Anti-reflux Venous Valve Endoprosthesis) clinical study.

The SAVVE study is a prospective, non-blinded,

single arm, multi-center study of seventy-five (75) CVI patients enrolled at 21 U.S.

endpoints for the SAVVE pivotal study include rVCSS scores, which will be used to provide evidence of clinically meaningful benefit,

as well as reflux time measurements, VAS pain scores, quality of life measurements, ulcer healing (for CEAP class C6 patients), and intra-operative

and one-year vein patency and valve functionality.

Safety endpoints include device related events and procedure related events –including mortality, pulmonary embolism, ipsilateral deep vein thrombosis, infection and bleeding.

first patient in the SAVVE pivotal study was enrolled in October of 2021.

Following enrollment of the first patient the SAVVE study was

delayed due to COVID-19 restrictions.

In November of 2022, we announced we 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 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.

October 6, 2023, we announced we had achieved full enrollment (75 subjects) in the SAVVE trial, having enrolled eighteen (18) patients

over the final two (2) months of the study.

Full enrollment occurred approximately four (4) months earlier than expected due to increased

demand for the VenoValve.

November 16, 2023, we presented positive preliminary device related Material Adverse Event (MAE) data at the 50th Annual VEITH

The preliminary device related MAE rate for the fully enrolled 75 subject study was eight percent (8%).

SAVVE study are defined as all-cause mortality, pulmonary embolisms (PEs), ipsilateral deep vein thromboses (DVTs), bleeding, and

deep wound infections, occurring within thirty (30) days of enrollment in the study.

The report on MAEs presented at the conference

indicated no deaths, no pulmonary embolisms, and six (6) deep vein thromboses (DVTs), from the fully enrolled cohort of 75

All DVTs were adjudicated as being mild in severity.

Left untreated, post-thrombotic patients with severe CVI are

known to DVT recurrence rates as high as eighteen percent (18%) at one year.

expect to release initial, topline rVCSS efficacy data from the SAVVE study at the VENOUS2024 American Venous Forum Annual Meeting on March 6, 2024.

With the FDA indicating that one-year

data for all 75 patients will be necessary prior to the filing of the application seeking pre-market (PMA) approval for the VenoValve,

the Company will be eligible to file the PMA application seeking approval in Q4 of 2024.

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.

Initial preliminary bench testing and pre-clinical testing for enVVe have been successfully

October 6, 2023, contemporaneously with the announcement of a twenty-eight-million-dollar capital raise, we announced plans to

expedite the development of enVVe.

The Company expects to begin a six (6) month Good Laboratory Practice animal study for enVVe in the

first quarter of 2024 and to be ready to file for IDE approval for the enVVe pivotal trial, the Transcatheter Anti-Reflux, Venous

Valve Endoprosthesis or TAVVE, by the end of 2024.

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 may otherwise not be good candidates for a surgical device, and estimate the U.S.

market for enVVe to be approximately 3.5 million

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

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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

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.

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.

The VenoValve will require the approval of a 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 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.

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.

Both the VenoValve and enVVe will require the approval of a PMA.

Trials in Support of PMA

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approved, for the following reasons:

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

manufacturing and sterilization of our biologic tissue devices.

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, or cGMP, and manufacturing and shipping for Class III medical devices, including biologic cardiovascular

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.

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.

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.

possess an extensive proprietary processing and manufacturing methodology specifically applicable to the design, processing, manufacturing

6 unchanged sentences

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

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.

We currently have twenty-six (26) patents

granted from agencies around the world including seven (7) from the USPTO.

of February 27, 2024, we had thirty-one (31) full-time employees.

None of our employees are represented by a collective bargaining

9 unchanged sentences

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