What changed in this filing

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Item 1. Business

2024-02-09 compared with 2023-02-10 · 148 added, 118 removed, 725 unchanged (27% of the section changed)

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We estimate that there are approximately 26 million people globally suffering from HF, including approximately 6.2 million people in the U.S.

and 8.6 million people in European Five.

and 8.6 million people in the European Five.

Every year, 1.3 million and 1.4 million new patients are diagnosed with HF in the U.S.

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Our BeAT-HF pivotal trial demonstrated compelling safety and effectiveness data regarding the clinical benefits of Barostim for HFrEF.

The pre-market data demonstrated safety and effectiveness leading to FDA approval, and safety and effectiveness were confirmed by the post-market data.

These results showed significant improvement in the following patient-centered outcomes:

• Quality of life (measured by Minnesota Living with Heart Failure (“MLWHF”)):

Our therapy demonstrated a 14-point improvement in quality of life for patients in the device arm relative to patients in the control arm.

A 5-point improvement is considered clinically meaningful.

• Exercise capacity (measured by the standardized 6 Minute Hall Walk (“6MHW”) distance test):

Our therapy demonstrated that patients in the device arm were able to improve the distance they walked in a six-minute period by 60 meters more than patients in the control arm.

Our therapy demonstrated that patients in the Barostim group were able to improve the distance they walked in a six-minute period by 56 meters and 44 meters more than patients in the Control group at six months and at one year, respectively, following implant, meaning the improvement was sustained.

A 25-meter improvement in walking distance is considered clinically meaningful.

• Quality of life (measured by Minnesota Living with Heart Failure (“MLWHF”)):

Our therapy demonstrated a 14-point, 8-point and 10-point improvement in quality of life for patients in the Barostim group relative to patients in the Control group at 6 months, 1 year and 2 years following implant, again demonstrating sustained improvement.

A 5-point improvement is considered clinically meaningful.

• Functional status (determined by New York Heart Association (“NYHA”) classification):

Our therapy demonstrated that 65% of patients in the device arm improved at least one NYHA class as compared to only 31% in the control arm, with 13% of patients improving two NYHA classes in the device arm as compared to only 2% in the control arm.

Our therapy demonstrated the following improvements in NYHA functional status versus the Control group at the specific points in time, meaning Barostim demonstrated greater and sustained improvement:

at 6 months, 67% in the BAT+ group and 37% in the Control group, favoring the BAT+ group by 30 percentage points;

at 1 year, 73% in the BAT+ group and 41% in the Control group, favoring the BAT+ group by 32 percentage points;

and, at 2 years, 68% in the BAT+ group and 41% in the Control group, favoring the BAT+ group by 27 percentage points.

• Freedom from All-Cause Death, LVAD, or Transplant.

Patients in the Barostim group had a directionally favorable 34% reduction in all-cause death or the use of LVAD or heart transplant versus the Control group.

• Improvement in Hierarchical Composite Outcomes.

Based on a hierarchical composite outcomes analysis (including cardiovascular (“CV”) mortality, LVAD/transplant, HF hospitalization and quality of life), the Win Ratio (defined below) was 1.26 in favor of the Barostim group.

In summary, the primary safety endpoint in the pre-market phase was previously met and subsequently confirmed in the post-market phase.

In the pre-market phase, all effectiveness endpoints were previously met, demonstrating 6-month improvements in 6MHW, quality of life, NYHA Class and NT-proBNP (described below).

The post-market phase effectiveness primary endpoint of CV mortality and HF hospitalization was not met.

Additional post-market phase effectiveness analyses (Win Ratio, freedom from all-cause mortality) suggested a favorable effect of Barostim Therapy.

The totality of the 6, 12 and 24-month data demonstrated symptomatic improvements for HF patients who are NYHA Class III or Class II (who had a recent history of Class III) despite treatment with guideline-directed therapies and who have a left ventricular ejection fraction ≤ 35% and a NT-proBNP<1600 pg/ml.

• Widely accepted mechanism of action.

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• Minimally invasive implant procedure.

Barostim’s implantable pulse generator (“IPG”) and stimulation lead are implanted during a minimally invasive procedure typically performed in an outpatient setting that lasts approximately one hour and involves two small skin incisions.

Barostim’s implantable pulse generator (“IPG”) and stimulation lead are implanted during a minimally invasive implant procedure typically performed in an outpatient setting that lasts approximately one hour and involves two small skin incisions.

Our device does not require hardware to be implanted in the heart or vasculature, which is the case with most other device-based treatments indicated for different HFrEF patient populations.

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• Potential reduction in total healthcare costs for HFrEF patients.

A Company-sponsored and co-authored cost-impact analysis, which was published in BMC Cardiovascular Disorders , a peer-reviewed manuscript, predicted that BAT plus GDMT would become the lower-cost alternative treatment within three years from implantation, as compared to GDMT alone, resulting in significant cost savings to healthcare systems.

A Company-sponsored and co-authored cost-impact analysis, which was published in BMC Cardiovascular Disorders , a peer-reviewed manuscript, predicted BAT plus GDMT would become the lower-cost alternative treatment within three years from implantation, as compared to GDMT alone, resulting in significant cost savings to healthcare systems.

• Inherent patient compliance and durability.

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We have developed a significant clinical data set that demonstrates the safety, effectiveness, patient adherence and durable benefits of Barostim Therapy.

Our BeAT-HF pivotal trial, which was a multi-center, prospective, randomized, controlled trial, met the primary safety and effectiveness endpoints and

demonstrated meaningful improvement in the quality of life, both physically and emotionally, for patients suffering from HFrEF.

Our BeAT-HF pivotal trial, which was a multi-center, prospective, randomized, controlled trial, met the primary safety and effectiveness endpoints and demonstrated meaningful improvement in the quality of life, both physically and emotionally, for patients suffering from HFrEF.

These results led to FDA Premarket Approval (“PMA”) approval of Barostim in August 2019 on an accelerated basis of only four months from the submission of the clinical trial report.

The BeAT-HF pivotal trial continued enrolling patients in the post-market stage of the trial in order to determine if Barostim demonstrates a statistically significant improvement in morbidity and mortality in patients with HFrEF.

We recently reached the required 320th event of the BeAT-HF clinical trial, and we expect to be able to unblind and announce data from this trial in the first quarter of 2023.

In addition to the morbidity and mortality endpoint, we have pre-specified a few potentially meaningful secondary and ancillary endpoints and analyses, in all cases designed to support FDA approval for additional claims related to Barostim Therapy, regardless of whether the primary endpoint is met.

We believe that any additional claims would have a positive impact on adoption of Barostim.

If we receive positive morbidity and mortality data from the post-market stage of the BeAT-HF pivotal trial, we plan to request that the FDA add the claim “Treatment for Heart Failure” to our current indication.

We believe this would increase our annual market opportunity in the U.S.

by an estimated $2.2 billion, or by 88,000 additional patients.

The BeAT-HF pivotal trial continued enrolling patients in the post-market stage of the trial in order to gather and evaluate additional, long-term data.

In December 2023, the FDA approved expanded labeling for Barostim based on the BeAT-HF trial data, resulting in simplification and clarification of the indications for use, as well as inclusion of the primary endpoint results, the 6, 12 and 24 month symptomatic data, the Win Ratio and the all-cause mortality data in the “Clinical Summary” discussion included in Barostim’s indications for use.

We currently believe our annual market opportunity in the U.S.

is an estimated $2.2 billion, or 76,000 patients, based on this new long-term safety and effectiveness data as well as our commercial experience and, as discussed below, the new reimbursement assignment for Barostim in 2024.

We continue to develop and expand upon our significant body of published clinical evidence that supports the meaningful benefits of Barostim Therapy.

We have also established a U.S.

patient registry to evaluate and assess real world outcomes from HFrEF patients who have been implanted with Barostim.

We are continuing to collect data through the U.S.

patient registry that we have established in order to evaluate and assess real world outcomes from HFrEF patients who have been implanted with Barostim.

We primarily sell Barostim to hospitals through a direct sales organization in the U.S.

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We support all aspects of the patient journey, which includes initial diagnosis, surgical support and patient follow-up.

We also highlight our compelling clinical benefits and value proposition to build awareness and adoption among physicians through targeted key opinion leader (“KOL”) development, referral network education and direct-to-consumer marketing.

We also highlight our compelling clinical benefits and value

proposition to build awareness and adoption among physicians through targeted key opinion leader (“KOL”) development, referral network education and direct-to-consumer marketing.

We utilize direct communication channels to inform and educate patients about Barostim Therapy and utilize a qualification process to aid in the identification of the appropriate patients for our therapy.

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We generated revenue of $39.3 million, a gross margin of 84% and a net loss of $41.2 million for the year ended December 31, 2023, compared to revenue of $22.5 million, a gross margin of 78% and a net loss of $41.4 million for the year ended December 31, 2022.

Revenue for 2021 and continuing into the first quarter of 2022 was negatively impacted by a decline in procedure volumes due to the Delta and Omicron variants of COVID-19 in the third and fourth quarters of 2021 and continuing into the first quarter of 2022.

By March 2022 and continuing through the date of this Annual Report on Form 10-K, implant centers resumed procedures at

more normal levels.

Our accumulated deficit as of December 31, 2023 and 2022, was $477.4 million and $436.2 million, respectively.

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The sympathetic system of the ANS is responsible for preparing the body for action through the “fight or flight” response.

When the body perceives a threat in the environment, the sympathetic system reacts by increasing the heart rate, widening the airways to allow for easier breathing, releasing stored energy, increasing strength in the muscles and slowing digestion and other bodily processes that are not as critical for taking action.

When the body perceives a threat in the environment, the sympathetic system reacts by increasing

the heart rate, widening the airways to allow for easier breathing, releasing stored energy, increasing strength in the muscles and slowing digestion and other bodily processes that are not as critical for taking action.

These changes prepare the body to respond appropriately to a threat in its environment.

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These two systems are strongly influenced by baroreceptors that are located in certain arterial walls.

The baroreceptors regulate the baroreflex, which is one of the body’s homeostatic mechanisms that help to

maintain blood pressure at nearly constant levels.

The baroreceptors regulate the baroreflex, which is one of the body’s homeostatic mechanisms that help to maintain blood pressure at nearly constant levels.

Baroreceptors provide beat-by-beat regulation of the body’s circulatory system by sending electrical signals to the brain.

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The majority of patients are initially identified as NYHA Class I or II and typically progress into subsequently worse states of the disease despite current treatment options.

On average, patients who

progress to a NYHA Class III either worsen to Class IV or die after 3.3 years.

On average, patients who progress to a NYHA Class III either worsen to Class IV or die after 3.3 years.

HFrEF patients are typically classified as NYHA Class II (moderate) or Class III (severe).

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• Co-morbidities / clinical fit:

A patient’s co-morbidities, such as severe chronic obstructive pulmonary disease (COPD), kidney disease or carotid stenosis, as well as a patient’s physical and psychological fit contribute to a physician’s treatment recommendation given the use of general anesthesia in most HF-related device-based treatment options.

A patient’s co-morbidities, such as severe chronic obstructive pulmonary disease (COPD), kidney disease or carotid stenosis, as well as a patient’s physical and psychological fit

contribute to a physician’s treatment recommendation given the use of general anesthesia in most HF-related device-based treatment options.

• QRS complex:

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Barostim’s market opportunity

We estimate that our initial annual market opportunity for HFrEF is $2.9 billion.

This includes a $1.4 billion initial market opportunity (55,000 HFrEF patients) in the U.S., and a $1.5 billion initial market opportunity (61,000 HFrEF patients) in the European Five.

In 2021, we estimated that our annual market opportunity for HFrEF was $2.9 billion, including a $1.4 billion initial market opportunity (55,000 HFrEF patients) in the U.S., and a $1.5 billion initial market opportunity (61,000 HFrEF patients) in the European Five.

In late 2023, we revised our U.S.

annual market opportunity – based on the new long-term safety and effectiveness data of BeAT-HF, our commercial experience and to account for the new reimbursement assignment for Barostim – to $2.2 billion, or 76,000 new patients.

Thus, we believe our global annual market opportunity for HFrEF is $3.7 billion.

We developed our Barostim platform technology to transform the treatment of HFrEF and other cardiovascular diseases and become the standard of care for this vulnerable and underpenetrated patient population.

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Patient selection

Barostim is indicated for the improvement of symptoms of HFrEF — quality of life, 6MHW and functional status — for patients who remain symptomatic despite treatment with GDMT, are NYHA Class III or II (who had a recent history of Class III), have a left ventricular ejection fraction ≤ 35%, a NT-proBNP < 1600 pg/ml and are not indicated for CRT according to the American Heart Association (“AHA”)/American College of Cardiology (“ACC”)/European Society of Cardiology (“ESC”) guidelines.

Barostim is indicated for patients who are NYHA Class III or II (who had a recent history of Class III) despite treatment with guideline-directed medical therapies (medications and devices), have a LVEF ≤ 35% and a NT-proBNP < 1600 pg/ml.

Barostim delivers Baroreflex Activation Therapy to improve patients’ NYHA functional status, 6MHW and quality of life.

Once a patient is diagnosed with HFrEF and recommended for an ICD and/or CRT, interventional or general cardiologists will often refer them to EPs, who often conduct a series of diagnostic tests, including an electrocardiogram, ultrasound and various blood tests, from which they will determine the patient’s eligibility for our therapy.

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• Addresses significant unmet medical need.

Barostim addresses a life-threatening disease for patients who failed to receive adequate benefits from existing treatments and who have no alternative treatment

Barostim addresses a life-threatening disease for patients who failed to receive adequate benefits from existing treatments and who have no alternative treatment options.

Based on this, the FDA granted Barostim a Breakthrough Device designation for HFrEF in June 2015.

• Safe and effective treatment.

Our clinical trial results demonstrated compelling safety and effectiveness data regarding the HFrEF clinical benefits of Barostim.

These results showed significant improvement in the following HF patient-centered outcomes:

• Quality of life (measured by MLWHF):

Our therapy demonstrated a 14-point improvement in quality of life for patients in the device arm relative to patients in the control arm.

A 5-point improvement is considered to be clinically meaningful.

Our BeAT-HF pivotal trial demonstrated compelling safety and effectiveness data regarding the clinical benefits of Barostim for HFrEF.

The pre-market data demonstrated safety and effectiveness leading to FDA approval and safety and effectiveness were confirmed by the post-market data.

These results showed significant improvement in the following patient-centered outcomes:

• Exercise capacity (measured by the standardized 6MHW distance test):

Our therapy demonstrated that patients in the device arm were able to improve their walking distance in a six-minute period by 60 meters more than that of patients in the control arm.

A 25-meter improvement in walking distance is considered to be clinically meaningful.

A 25-meter improvement in walking distance is considered clinically meaningful.

• Quality of life (measured by MLWHF):

A 5-point improvement is considered clinically meaningful.

• Functional status (determined by NYHA classification):

Our therapy demonstrated that 65% of patients who were in the device arm improved at least one NYHA class as compared to only 31% in the control arm, with 13% of patients improving two NYHA classes in the device arm as compared to only 2% in the control arm.

• NT-proBNP (Serum biomarker used as indicator of severity of HF):

Our therapy demonstrated that patients in the device arm had a 25% improvement in NT-proBNP relative to that of patients in the control arm.

A 10% improvement is considered to be clinically meaningful.

Our therapy demonstrated the following improvements in NYHA functional status versus the Control group at the specific points in time, meaning Barostim demonstrated greater and sustained improvement:

at 6 months, 67% in the BAT+ group and 37% in the Control group, favoring the BAT+ group by 30 percentage points;

at 1 year, 73% in the BAT+ group and 41% in the Control group, favoring the BAT+ group by 32 percentage points;

and, at 2 years, 68% in the BAT+ group and 41% in the Control group, favoring the BAT+ group by 27 percentage points.

• Freedom from All-Cause Death, LVAD, or Transplant.

Patients in the Barostim group had a directionally favorable 34% reduction in all-cause death or the use of LVAD or heart transplant versus the Control group.

• Improvement in Hierarchical Composite Outcomes.

Based on a hierarchical composite outcomes analysis (including CV mortality, LVAD/transplant, HF hospitalization and quality of life), the Win Ratio was 1.26 in favor of the Barostim group.

The significant benefits of our therapy were observed despite a four-fold uptake of ARNI medication in the control arm, as compared to the device arm.

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• Potential reduction in total healthcare costs for HFrEF patients.

In addition to providing improved physical and health-related benefits and quality of life for patients, we estimate Barostim has the potential to

result in cost savings to healthcare systems.

In addition to providing improved physical and health-related benefits and quality of life for patients, we estimate Barostim has the potential to result in cost savings to healthcare systems.

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Barostim ensures patient compliance, unlike most commercially available drug treatments, as it requires no device interaction by the patient.

Our device has a battery that does not require recharging, has an average service life of five years and is replaced through a short outpatient procedure.

Our device has a battery that does not require recharging, has an average service life of five to six years and is replaced through a short outpatient procedure.

Clinical results and studies

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We designed our BeAT-HF (Phase III) pivotal trial in collaboration with the FDA under the Breakthrough Devices Program, which was implemented to accelerate the approval of novel therapies targeting unmet needs for debilitating or life-threatening conditions.

Our BeAT-HF pivotal trial met the primary safety and effectiveness endpoints and demonstrated meaningful improvement in the quality of life, both physically and emotionally, for patients suffering from HFrEF.

The pre-market phase of our BeAT-HF pivotal trial met the primary safety and effectiveness endpoints and demonstrated meaningful improvement in the quality of life, both physically and emotionally, for patients suffering from HFrEF.

These results led to the FDA approval of Barostim in August 2019 on an accelerated basis of only four months from the submission of the final clinical trial report.

Barostim is indicated for the improvement of symptoms of HFrEF — quality of life, 6MHW and functional status — for patients who remain symptomatic despite treatment with GDMT, are NYHA Class III or Class II (with a recent history of Class III), have a LVEF ≤ 35%, a NT-proBNP < 1,600 pg/ml and excluding patients indicated for CRT according to AHA/ACC/ESC guidelines.

The post-market phase BeAT-HF pivotal trial met the primary safety endpoint, and although it did not meet the primary effectiveness endpoint, showed sustained improvements in exercise capacity, quality of life and NYHA functional status, and favored Barostim in freedom from all-cause mortality, LVAD or transplant and in the Win Ratio.

This led to the FDA approval of expanded labeling with these results and a simplification and clarification of the following indications for use.

Barostim is indicated for patients who are NYHA Class III or Class II (with a recent history of Class III) despite treatment with guideline-directed medical therapies (medications and devices), have a LVEF ≤ 35% and a NT-proBNP < 1,600 pg/ml.

Barostim delivers Baroreflex Activation Therapy to improve patients’ NYHA functional status, 6MHW and quality of life.

The safety and effectiveness of Barostim Therapy have been published in more than 60 peer-reviewed publications, approximately 20 of which relate to the treatment of HF, including, among others, the publication of the pivotal trial results in the Journal of the American College of Cardiology.

The table below summarizes the clinical measurements, results and outcomes from our HF trials, including improvements in HF symptoms, patient-reported quality of life measures and our therapy’s favorable safety profile.

We have established a U.S.

patient registry to evaluate and assess real world patient outcomes from patients who have been implanted with Barostim.

Investment in clinical evidence continues to be one of our core

strategies, and we intend to continue to develop and expand upon a significant body of published clinical evidence that supports the safety and effectiveness of Barostim Therapy.

Investment in clinical evidence continues to be one of our core strategies, and we intend to continue to develop and expand upon a significant body of published clinical evidence that supports the safety and effectiveness of Barostim Therapy.

Pivotal Phase III Study:

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(1) A pre-market stage that examined three primary effectiveness endpoints (quality of life, 6MHW and NT-proBNP), as well as one safety endpoint that included the major adverse neurological or cardiovascular system or procedure-related event rate (“MANCE”).

(2) A post-market stage to examine the effects of BAT on rates of HF hospitalization and cardiovascular mortality and potentially expand the indication for Barostim.

(2) A post-market stage that examined the effects of BAT on rates of HF hospitalization and cardiovascular mortality, as well as sustained safety and symptomatic improvements, which expanded the labeling for Barostim.

Patients were eligible for the trial if they were NYHA Class III or Class II (with a recent history of Class III);

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and were an acceptable surgical candidate.

Patients who had AHA/ACC/ESC Class I indication for a CRT were excluded, and there were no restrictions for atrial fibrillation or atrial flutter.

Trial results

Patients who had a Class I indication for a CRT according to the American Heart Association/American College of Cardiology/European Society of Cardiology guidelines were excluded, and there were no restrictions for atrial fibrillation or atrial flutter.

In summary, the primary safety endpoint in the pre-market phase was previously met and confirmed in the post-market phase.

In the pre-market phase, all effectiveness endpoints were previously met, demonstrating 6-month improvements in 6MHW, quality of life, NYHA Class and NT-proBNP.

The post-market phase effectiveness primary endpoint of CV mortality and HF hospitalization was not met.

Additional post-market phase effectiveness analyses (Win Ratio and freedom from all-cause mortality) suggested a favorable effect of Barostim Therapy.

The totality of the 6, 12 and 24-month data demonstrated symptomatic improvements

for HF patients who are NYHA Class III or Class II (who had a recent history of Class III) despite treatment with guideline-directed therapies and who have a LVEF ≤ 35% and a NT-proBNP < 1600 pg/ml.

Pre-market phase results

The safety and effectiveness data in the BeAT-HF pivotal trial support the HFrEF clinical benefits of Barostim.

These results demonstrated that BAT is safe in patients with HFrEF and significantly improves the patient-centered symptomatic endpoints of the quality-of-life score, 6MHW and functional status, as well as the confirmatory nature of the evidence provided by a reduction of NT-proBNP.

These results demonstrated that BAT is safe in patients with HFrEF and significantly improves the patient-centered symptomatic endpoints of the quality-of-life score, 6MHW and NYHA functional status, as well as the confirmatory nature of the evidence provided by a reduction of NT-proBNP.

• Quality of life (measured by MLWHF):

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0.10 to 0.73) and there were no significant differences in blood pressure or heart rate.

We recently reached the required 320 th event of the BeAT-HF clinical trial, and we expect to be able to unblind and announce data from this trial in the first quarter of 2023.

Post-market phase results

The BeAT-HF pivotal trial continued enrolling patients in the post-market stage of the trial to determine if Barostim demonstrates a statistically significant improvement in morbidity and mortality in patients with HFrEF.

Between May 2019 and July 2020, an additional 59 adult patients were randomized at 17 sites within the U.S.

as part of the post-market phase of the trial.

The safety and effectiveness data in the BeAT-HF pivotal trial support the HFrEF clinical benefits of Barostim.

These results demonstrated that BAT is safe in patients with HFrEF, showed a directional reduction in the primary endpoint of CV mortality and HF morbidity (although not reaching statistical significance), and favored patient-centered symptomatic improvements at 6 and 12 months in 6MHW and at 6,12 and 24 months in the MLWHF quality of life and NYHA Class.

• Exercise capacity (measured by the standardized 6MHW distance test):

The BAT+ group showed an improvement at both 6 and 12 months compared to the Control group.

The difference between the arms at 6 months was 56 meters and at 12 months the difference was sustained with 44 meters.

These improvements between the groups are not only statistically significant, but they are approximately twice the clinically significant value of 25 meters.

• Quality of life (measured by MLWHF):

The BAT+ group showed a decrease (improvement) in quality of life points ranging from 17 to 20 points from baseline across the follow-up visits.

The differences between the groups at 6, 12 and 24 months are -14, -8 and -10, respectively, which is not only statistically significant, but is greater than a clinically meaningful difference of 5 points.

• Functional status (determined by NYHA classification):

Approximately two-thirds of the BAT+ group improved at least one NYHA class across the follow-up visits.

Additionally, the percentage of subjects improving between the arms at 6, 12 and 24 months was higher in the BAT+ group compared to the Control group.

• Hierarchical Win Ratio:

The hierarchical composite analysis using the Win Ratio was evaluated using the components of the CV morbidity and HF mortality endpoints and the MLWHF quality of life (CV mortality, heart transplant or LVAD, number of hospitalizations or emergency visits for HF, number of unscheduled clinical visits with IV diuretic and change from baseline in MLWHF at 12 months).

This resulted in a Win Ratio of 1.26, reflecting beneficial trend in the heart transplant/LVAD over the course of the study and MLWHF at 12 months.

• Freedom from All-Cause Mortality:

In addition to the results above, freedom from all-cause mortality (all-cause death, LVAD and heart transplant) demonstrated a 34% reduction between the groups.

In the BAT+ group, the crude event rate was 7.0 per 100 years with 38 events during 544 patient-years at risk.

In the Control group, the crude event rate was 10.4 per 100 years with 51 events during 492 patient-years at risk.

As shown below, the hazard ratio for all-cause mortality = 0.662 (95% CI 0.435, 1.007), representing a relative risk reduction of 34% in the BAT+ group compared with the Control group.

The hazard ratio for all-cause mortality using a per protocol analysis = 0.589 (95% CI 0.380, 0.923), representing a relative risk reduction of 41% in the BAT+ group compared with the Control group.

The system or procedure related MANCE endpoint includes all events that occurred across the duration of follow-up.

The analysis includes subjects in BAT+ group who had an implant attempted (n=159), representing 6,664 total months of implant follow-up.

All implant attempts were successful.

As shown below, the MANCE-free rate is 96.9%, with 154 out of 159 implanted patients being event free with a lower bound one-sided 95% confidence level of 93.5% (p value <0.001 compared to a performance goal of 85%).

Phase II Study:

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This study provided the first evidence that chronic stimulation of carotid baroreceptors markedly and persistently reduced the sympathetic activation characterizing HF patients.

It also demonstrated that the reduction is accompanied by the improvement of a major modulator of sympathetic activity, the arterial baroreflex and baroreflex activation is accompanied by favorable therapeutic impact on cardiac function and clinical profile, as shown in the improved quality of life, increased exercise tolerance and improved functional status.

Other clinical trials

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In March 2020, after review of early clinical data and the competitive landscape, the FDA granted a Breakthrough Device designation for Barostim for the treatment of HFpEF.

In 2023, the FDA admitted us into the Total Life Cycle Advisory Program (“TAP”) for Barostim’s treatment of HFpEF.

TAP is an initial pilot program limited only to Breakthrough Device designated indications for new products.

Sales and marketing

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and an Active Implantable Medical Device Directive (“AIMDD”) CE Mark for the treatment of HFrEF and resistant hypertension in Europe.

The AIMDD CE Mark certificate expired in December 2022, as expected during the process of transitioning to the MDR.

The MDR transition rules provide that product available in the market at the time of AIMDD CE Mark expiration can be sold through 2025.

We have placed approximately one year’s worth of European product in the market to support sales through the end of 2023.

If CVRx does not obtain MDR approval prior to exhausting our product currently in the European market, or the EEA does not grant further extensions under the MDR transition rules prior to CVRx obtaining MDR approval, then CVRx will not be able to continue to sell in Europe until MDR approval or another extension is granted.

Additionally, the EU approved an amendment to the MDR (as defined below) which allows qualifying AIMDD CE certificates to be accepted through December of 2027.

We have already met the qualifications identified within this amendment to allow continued distribution of Barostim through this time.

We market our therapy in the U.S.

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Coding and payment in the United States

In the U.S., we sell Barostim primarily to hospitals, where the device is implanted in an outpatient setting.

In the U.S., we sell Barostim primarily to hospitals, where the device is implanted in outpatient and inpatient settings.

Our customers bill various third-party payors, such as government agencies, administrative contractors, commercial payors and integrated managed care organizations, for the cost required to treat each patient.

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Physician reimbursement under Medicare is generally based on a defined fee schedule, the Physician Fee Schedule, through which payment amounts are determined by the relative values of the professional services rendered.

Medicare provides reimbursement to hospitals using Barostim under the hospital outpatient prospective system (“HOPPS”), which provides bundled amounts generally intended to reimburse a hospital for all facility costs related to procedures performed in its outpatient setting.

Under the HOPPS, the national Medicare payment to a hospital for a new patient implant or an IPG replacement is paid using the Level 5 Neurostimulator payment code APC 5465, which has a national average of $29,358 in 2023.

Medicare provides reimbursement to hospitals using Barostim under the hospital outpatient prospective system (“OPPS”), which provides bundled amounts generally intended to reimburse a hospital for all facility costs related to procedures performed in its outpatient setting.

Under the OPPS in 2023, the national Medicare payment to a hospital for a new patient implant or an IPG replacement is paid using the Level 5 Neurostimulator payment code APC 5465, which has a national average of $29,358.

Under the 2024 OPPS final rule, Barostim was reassigned to New Technology APC 1580, which carries an average payment amount of $45,000, and took effect January 1, 2024.

Payment codes such as APC 1580 are indexed to adjust for cost of living and thus vary by location.

These payments generally cover the hospital’s costs for the device and the implantation procedure.

CMS also granted a TPT payment for the implantation of Barostim in an outpatient setting, which took effect in January 2021 and expires at the end of 2023.

The TPT payment is an incremental payment for new and innovative technologies that meet certain qualifications.

It allows hospitals to bill for a pass-through of the device cost, which includes up to $35,000, and can be added to the procedure costs.

CMS had also granted a TPT payment for the implantation of Barostim in an outpatient setting, which took effect in January 2021 and expired at the end of 2023.

The TPT payment was an incremental payment for new and innovative technologies that meet certain qualifications.

It allowed hospitals to bill for a pass-through of the device cost, which included up to $35,000, and could be added to the procedure costs.

We anticipate inpatient procedures to continue to represent a small percentage of our sales.

For these inpatient procedures, ICD-10-PCS codes 0JH60MZ + 03HL3M are commonly mapped into Diagnosis Related Group (“DRG”) 252, which has an established national average Medicare payment of $23,482 in 2024.

CMS also granted an NTAP that was added to the DRG from October 2020 through October 2022 to cover the implantation of Barostim in an inpatient setting.

The NTAP is an incremental inpatient payment for new and innovative technologies that meet certain qualifications.

This payment allowed hospitals to be reimbursed an additional $22,750 (65% of the total cost of the device).

The surgeon implanting Barostim is paid an additional physician payment under the Medicare Physician Fee Schedule, and the physician that manages the device performs multiple device interrogations and is paid using the payment code APC 5721, which has a national average of $149 per visit in 2024.

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Since approximately 67% of our target treatment population includes Medicare-eligible patients, we have prioritized CMS coverage while simultaneously developing processes to engage commercial payors.

As of July 2020, all MACs have retired automatic coverage denial policies, thereby allowing hospitals to be paid for our procedure.

As of July 2020, all Medicare Administrative Contractors (“MACs”) have retired automatic coverage denial policies, thereby allowing hospitals to be paid for our procedure.

CMS has committed to considering additional process improvements to increase access to innovative devices.

We will continue to monitor developments in this space, including decisions made by private payors, if any.

We will continue to leverage our in-house market access team to obtain appropriate prior authorization approvals in advance of treatment on a case-by-case basis where positive coverage policies currently do not

We believe our market access team is highly effective in obtaining prior authorizations, including navigating the appeals process.

We believe that we will continue to benefit from this efficient prior authorization process in the near-and-long-term by expanding on our positive coverage policies with commercial payors.

In our discussions with commercial payors, we highlight our compelling and robust clinical data, the potential economic cost-savings associated with our highly compliant treatment, increased patient demand and support from leading medical societies and KOLs.

In our discussions with commercial payors, we highlight our compelling and robust clinical data, including the long-term post-market BeAT-HF data, the potential economic cost-savings associated with our highly compliant treatment, increased patient demand and support from leading medical societies and KOLs.

As our operations continue to grow, we intend to continue to further expand our market access team accordingly.

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We are also enrolling a clinical trial for a new implant toolkit called BATwire, which enables an ultrasound-guided procedure to implant Barostim and the use of local anesthetics.

This has the potential to expand our annual market opportunity in the U.S.

by an estimated $1 billion, or by 39,000 additional patients who are deemed clinically unfit for the current procedure.

This simplified procedure would also allow EPs to complete the procedure in an outpatient catheter lab center.

While we are currently focused on the treatment of patients with HFrEF, we believe our platform technology can provide meaningful benefits to a broader set of patients suffering from cardiovascular diseases with significant unmet needs.

Our longer-term goal is to explore Barostim’s potential to expand the indications for use to other cardiovascular diseases, including different forms of HF, hypertension and arrhythmias.

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However, CCM is associated with a number of drawbacks, including not being designed to address the imbalance of the ANS;

less favorable clinical effectiveness results in patients with LVEF 25–35% as compared to patients with LVEF 35–45% related to exercise capacity, quality of life and functional status;

less favorable clinical effectiveness results in patients with LVEF 25–35% as compared to patients with LVEF 35–45% related to exercise capacity, quality of life and NYHA functional status;

implantation through an invasive procedure that includes running electrical leads through the veins and attaching them to the heart’s ventricle, which may lead to increased risks to the patient;

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patent applications.

Outside of the U.S., we owned seven patents in multiple countries and had one pending application.

Outside of the U.S., we owned seven patents in multiple countries and had 14 pending applications.

Our trademark portfolio focuses on nine trademarks in the U.S.

and multiple other countries.

Our patents cover aspects of our integrated platform technology, Barostim, including baroreflex methods, stimulus regimes, mapping methods, electrode designs, disease treatments, closed loop control, burst intervals, connection structures and baroreceptor locations, as

well as future product concepts.

The term of individual patents depends on the law of the countries in which they are granted.

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We are registered with the FDA as a medical device manufacturer and licensed by the State of Minnesota to manufacture our device.

We expect that any revenue we generate could fluctuate from quarter to quarter as a result of timing and seasonality.

We expect that revenue could fluctuate from quarter to quarter as a result of timing and seasonality.

We anticipate mild seasonality based on national holiday patterns specific to certain nations.

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Class II devices are subject to the FDA’s General Controls, and special controls as deemed necessary by the FDA to ensure the safety and effectiveness of the device.

These special controls can include performance standards, post-market surveillance, patient registries and FDA guidance documents.

These special controls

can include performance standards, post-market surveillance, patient registries and FDA guidance documents.

While most Class I devices are exempt from the 510(k) premarket notification requirement, manufacturers of most Class II devices must submit to the FDA a premarket notification under Section 510(k) of the FDCA requesting permission to commercially distribute the device.

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The PMA 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.

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 must also contain a full description of the device and its components, and the methods, facilities and controls used for manufacturing and proposed labeling.

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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 typically does 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.

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 FDA will approve the new device for commercial distribution if it determines that the data and information in the HDE constitute valid scientific evidence and that there is reasonable assurance that the device is safe and has probable benefit for its intended use(s) according to the instructions for use or labeling.

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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 be approved prior to commencing human clinical trials.

A significant risk device is one that presents a potential for serious risk to the health, safety or welfare of a subject 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.

An IDE application must be supported by appropriate data showing that it is safe to test the device in humans and that the testing protocol is scientifically sound.

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A person or entity does not need to have actual knowledge of this statute or specific intent to violate it to have committed a violation;

property to the federal government or knowingly concealing, or knowingly and improperly avoiding or decreasing, an obligation to pay or transmit money to the federal government.

• the federal False Claims Act (and similar state laws) prohibiting, among other things, knowingly presenting, or causing to be presented, claims for payment or approval to the federal government that are false or fraudulent, knowingly making a false statement material to an obligation to pay or transmit money or property to the federal government or knowingly concealing, or knowingly and improperly avoiding or decreasing, an obligation to pay or transmit money to the federal government.

The government may assert that a claim includes items or services resulting from a violation of the federal Anti-Kickback Statute and thus constitutes a false or fraudulent claim for purposes of the false claims statute;

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We also received and responded to queries from all MDR sections, with the exception of Clinical Research, in 2022.

We have since received confirmation that the Clinical Research section, along with our query responses, is currently under review.

We believe these developments should result in completion of the Technical File review by the end of 2023.

Notably, a proposal by the European Commission is under consideration to extend existing AIMDD CE certificates through May 31, 2027.

This proposal is driven by delays in notified body reviews and approvals across the medical device industry as well as the fact that a substantial number of CE Mark certificates are continuing to expire during this unpredictable and extended transition period to MDR.

Given the need for devices in the EEA, it seems probable that the MDR transition rules will be modified by extension or some other means to allow continued sales of devices in the EEA beyond the currently available supply for medical devices, to the extent CVRx’s MDR approval is not completed in 2023.

We have since received confirmation that all sections of the submission have been reviewed and all queries have been responded to.

The file remains under review.

Notably, the European Commission extended qualifying AIMDD CE certificates, including ours, through December 31, 2027.

This extension was driven by delays in notified body reviews and approvals across the medical device industry as well as the fact that a substantial number of CE Mark certificates were continuing to expire during this unpredictable and extended transition period to MDR.

Regulation of medical devices under MDR

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To demonstrate compliance with the general safety and performance requirements, the manufacturer must undergo a conformity assessment procedure which requires the involvement of a Notified Body except for low-risk, self-certified medical devices of Class I.

The Notified Body typically audits the quality management system of the manufacturer, which must comply with the current version of ISO 13485 requiring that manufacturers to follow defined and approved design and development procedures, testing, control, documentation and other quality assurance procedures throughout the entire design and manufacturing process.

The Notified Body typically audits the quality management system of the manufacturer, which must comply with the current version of ISO 13485 requiring that manufacturers follow defined and approved design and development procedures, testing, control, documentation and other quality assurance procedures throughout the entire design and manufacturing process.

The Notified Body also reviews the Technical File that includes the Biological Evaluation, Clinical Evaluation and Risk Management reports and Post Market Clinical Follow-Up (PMCF), among other items, submitted for approval of the CE Mark.

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CE marking in UK and UK Conformity Assessed marking

Since January 1, 2021, the UK (excluding Northern Ireland) has recognized medical devices with an EEA-issued CE Mark, and will continue to do so until June 30, 2023.

Additionally, certificates issued by EU-recognized Notified Bodies will continue to be valid for the UK market until June 30, 2023.

Beginning on July 1, 2023, a UK Conformity Assessed (“UKCA”) marking will be required to place a device on the Great Britain market (England, Wales and Scotland).

The UKCA marking is a UK product marking used for certain goods, including medical devices, placed on the market in England, Wales and Scotland.

The UKCA marking is not recognized in the EU, EEA or Northern Ireland, so relevant products require a CE marking for sale in these markets.

Since January 1, 2021, the UK (excluding Northern Ireland) has recognized medical devices with an EEA-issued CE Mark, and has since indicated it will continue to do so until December 31, 2027.

Additionally, certificates issued by EU-recognized Notified Bodies will continue to be valid for the UK market until December 31, 2027.

Since January 1, 2021, all medical devices placed on the UK market must be registered with the Medicines and Healthcare products Regulatory Agency (the “MHRA”).

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Manufacturers based outside the UK who wish to place a device on the UK market need to appoint a single UK Responsible Person who will take responsibility for the product in the UK.

We have registered with MHRA, have a UK Responsible Person, and are prepared to conduct a conformity assessment when necessary.

CE Marking in Switzerland

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Product labeling should include the CH-REP name and address to show compliance.

MDD/AIMDD devices placed on the market before the certificate expiration date or by May 26, 2024, whichever occurs sooner.

These devices will continue to be available on the market until May 26, 2025.

We have engaged a CH-REP and, because we placed Barostim on the market prior to expiration of our AIMDD CE Mark, the devices may continue to be sold in Switzerland through 2023.

A pending proposal to accept either CE or FDA approval of devices would allow continued sales in Switzerland after 2023 should the MDR approval not be completed.

However, this proposal is not approved and detailed requirements are unclear.

MDD/AIMDD devices with certificates issued by EU-recognized Notified Bodies will continue to be valid until December 31, 2027.

We have engaged a CH-REP and the devices may continue to be sold in Switzerland through 2027.

Clinical investigation

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Post-market surveillance is comprised of, but not limited to, reports of serious adverse events, device deficiency reports, product complaints from consumers and health care professionals, field safety corrective actions and post-marketing clinical studies/updated clinical evaluation reports.

Manufacturers must guarantee that their medical device continues to provide the promised benefit to

patients as well as the lack of any unacceptable risks, through a constant and systematic approach to post-market surveillance.

Manufacturers must guarantee that their medical device continues to provide the promised benefit to patients as well as the lack of any unacceptable risks, through a constant and systematic approach to post-market surveillance.

Further, manufacturers, medical practitioners and medical institutions are obliged to report any incident involving a medical device, including any malfunction or deterioration in the characteristics and/or performance of a device, as well as any inadequacy in the labelling or the instructions for use which might lead to or might have led to the death of a patient or to a serious deterioration in his or her state of health.

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Department of Health and Human Services (“HHS”) issued regulations in July 1991, which HHS has referred to as “safe harbors.” These safe harbor regulations set forth certain provisions which, if met in form and substance, will assure medical device manufacturers, healthcare providers and other parties that they will not be prosecuted under the federal Anti-Kickback Statute.

Additional safe harbor provisions providing similar protections have been published intermittently since 1991.

Additional safe harbor provisions providing similar protections have been published intermittently

Although there are a number of statutory exceptions and regulatory safe harbors protecting some common activities from prosecution, the exceptions and safe harbors are drawn narrowly.

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Violations of the federal Anti-Kickback Statute may result in civil monetary penalties up to $100,000 for each violation, plus up to three times the remuneration involved.

Civil penalties for such conduct can further be

assessed under the federal False Claims Act.

Civil penalties for such conduct can further be assessed under the federal False Claims Act.

Violations can also result in criminal penalties, including criminal fines of up to $100,000 and imprisonment of up to 10 years.

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Foreign laws and regulations may vary greatly from country to country.

For example, the advertising and promotion of our products is

subject to EU Directives concerning misleading and comparative advertising and unfair commercial practices, as well as other EEA member state legislation governing the advertising and promotion of medical devices.

For example, the advertising and promotion of our products is subject to EU Directives concerning misleading and comparative advertising and unfair commercial practices, as well as other EEA member state legislation governing the advertising and promotion of medical devices.

These laws may limit or restrict the advertising and promotion of our products to the general public and may impose limitations on our promotional activities with healthcare professionals.

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In addition, if the PHI of 500 or more individuals is improperly used or disclosed, we would be required to report the improper use or disclosure to HHS, which would post the violation on its website, and to the media.

Failure to comply with the HIPAA privacy and security standards can result in civil monetary penalties up to $63,973 per

violation, not to exceed $1.92 million per calendar year for non-compliance of an identical provision and, in certain circumstances, criminal penalties with fines up to $250,000 per violation and/or imprisonment.

Failure to comply with the HIPAA privacy and security standards can result in civil monetary penalties up to $63,973 per violation, not to exceed $1.92 million per calendar year for non-compliance of an identical provision and, in certain circumstances, criminal penalties with fines up to $250,000 per violation and/or imprisonment.

HIPAA authorizes state attorneys general to file suit on behalf of their residents for violations.

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In addition, the FCPA imposes accounting standards and requirements on publicly traded U.S.

corporations and their foreign affiliates, which are intended to prevent the diversion of corporate funds to the payment of

bribes and other improper payments, and to prevent the establishment of “off books” slush funds from which such improper payments can be made.

corporations and their foreign affiliates, which are intended to prevent the diversion of corporate funds to the payment of bribes and other improper payments, and to prevent the establishment of “off books” slush funds from which such improper payments can be made.

We also are subject to similar anticorruption legislation implemented in Europe under the Organization for Economic Co-operation and Development’s Convention on Combating Bribery of Foreign Public Officials in International Business Transactions.

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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