Company Overview - CVRx has developed the world's first autonomic neuromodulation therapy specifically for the treatment of heart failure, targeting a significant market opportunity valued at $10.5 billion based on prevalence [1] - The company aims to establish this therapy as the standard of care for heart failure treatment, supported by a well-defined patient population and a highly differentiated therapeutic approach [1] Industry Context - Heart failure is a major health issue affecting nearly 6.7 million Americans, leading to over 1 million hospital discharges and emergency room visits annually, along with more than 8 million physician visits [2] - The financial burden of heart failure is substantial, with costs projected to reach nearly $70 billion per year by the end of the decade [2] Treatment Landscape - Current treatment for heart failure typically involves a combination of four drugs known as quad therapy, which is the guideline-directed Class 1 treatment [3] - A small percentage of heart failure patients are evaluated for cardiac resynchronization therapy (CRT), indicating a limited scope for existing pacing therapies [3]

Core Insights - Karolinska Development's portfolio company AnaCardio has reported positive results from the phase 2a clinical trial GOAL-HF1 for the drug candidate AC01, aimed at treating heart failure with reduced ejection fraction (HFrEF) [1][5] - The study met its primary endpoint, demonstrating a favorable safety and tolerability profile, and showed encouraging efficacy signals, leading to plans for a phase 2b trial [1][5] Company Overview - AnaCardio AB is a privately held Swedish biopharmaceutical company focused on developing novel drugs for heart failure [2] - Karolinska Development holds a 10 percent ownership stake in AnaCardio [6] Clinical Trial Details - The phase 2a study enrolled 26 patients across 13 European heart failure centers, with participants receiving either 1 mg or 3 mg of AC01 or a placebo twice daily for 28 days [3] - Exploratory efficacy assessments indicated rapid and sustained improvements in haemodynamics and cardiac structure and function over the treatment period [3] - The pharmacokinetics of AC01 were predictable and dose-proportional, with confirmed target engagement through a dose-dependent increase in growth hormone release [4] Safety Profile - No treatment-emergent adverse events leading to discontinuation or serious adverse events were reported, nor were there any clinically relevant effects on blood pressure [5] - The CEO of Karolinska Development expressed confidence in AC01's potential to transform heart failure treatment based on the study's strong data [5]

Financial Data and Key Metrics Changes - Total expenses decreased by 35% year-over-year to $8.1 million in 2024 from $12.1 million in 2023, primarily driven by a 43% reduction in research and development expenses to $4.4 million from $7.7 million [35][36] - Net loss decreased to $7.9 million in 2024, down from $11.6 million in 2023, with net cash used in operations approximately $8 million, a 20% decrease from $10 million in 2023 [37][38] - The company ended the year with cash and cash equivalents totaling $2.4 million, with expectations of a moderate increase in cash burn in 2025 [38] Business Line Data and Key Metrics Changes - The CARDI-AMP Heart Failure Trial showed a 47% relative risk reduction in heart death equivalents and a 16% relative risk reduction in major adverse cardiac events, with a clinically meaningful 10.5% improvement in quality of life score [14][19] - The trial did not meet its primary endpoint due to the six-minute walk distance test, but showed strong results in other key areas [12][19] Market Data and Key Metrics Changes - The market reaction to the trial results was surprising, as the data was in line with expectations, indicating a strong need for therapies in ischemic heart failure [18][22] - The FDA granted cardiac cell therapy a breakthrough device designation, highlighting the significant unmet clinical need in this area [22][24] Company Strategy and Development Direction - The company is focused on advancing its cardiac cell therapy programs, with plans to share two-year data with the FDA and Japan's PMDA to align on pathways for making therapies available [21][22] - Ongoing discussions with regulatory agencies aim to ensure the safety and efficacy of cardiac cell therapy, with a focus on the unique benefits of the therapy compared to traditional medical devices [24][29] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the strength of the data from the CARDI-AMP trial and its implications for future trials, particularly the CAR-DMHF2 trial [20][21] - The company anticipates modest increases in R&D expenses in 2025 as it continues to advance therapeutic candidates [36] Other Important Information - The company completed enrollment in the low-dose cohort of its cardi-allo-allogeneic mesenchymal stem cell therapy in ischemic heart failure [26] - The Helix biotherapeutic delivery platform is expected to enhance commercialization and clinical development efficiency [31][32] Q&A Session Summary Question: Can you provide more details on PMDA discussions in Japan? - Management met with PMDA in November and is preparing to share two-year data, which looks promising, potentially leading to conditional approval in Japan [42][43] Question: Were there any subsequent therapies that could have impacted the data read? - All patients were on guideline-directed medical therapy, and no other medications were introduced during the trial [46][48] Question: What is the expected timeline for sharing two-year data with the FDA? - The company is preparing a submission package and expects to request a consultation with the FDA soon, with timelines potentially ranging from three to eight weeks [78][80] Question: How does the data from the Heart Failure 1 trial inform the Heart Failure 2 trial? - The primary endpoint structure remains the same, and the company aims to replicate the positive outcomes seen in the first trial [88][90] Question: What are the next steps with the PMDA? - The company is finalizing the submission package and scheduling the next consultation with PMDA, aiming for a thorough and detailed presentation [78][82]

Financial Data and Key Metrics Changes - Total expenses decreased by 35% year-over-year to $8.1 million in 2024 from $12.1 million in 2023, primarily driven by a 43% reduction in research and development expenses to $4.4 million from $7.7 million [35][36] - Net loss decreased to $7.9 million in 2024, down from $11.6 million in 2023, and net cash used in operations was approximately $8 million, a 20% decrease from approximately $10 million in 2023 [37][38] - The company ended the year with cash and cash equivalents totaling $2.4 million, with expectations of a moderate increase in cash burn in 2025 [38] Business Line Data and Key Metrics Changes - The CARDI-AMP Heart Failure Trial data showed a 47% relative risk reduction in heart death equivalents and a 16% relative risk reduction in major adverse cardiac events [14][19] - Quality of life improvements were noted with a 10.5% point increase in quality of life scores and a 13.9-meter improvement in the six-minute walk distance test [14][15] Market Data and Key Metrics Changes - The market reaction to the trial results was unexpected, as the data was aligned with previous expectations despite not meeting the primary endpoint [18][19] - The company anticipates that the compelling data will enhance interest from distribution partners and strategics, particularly in the context of increasing attention on interventional therapies for heart failure [29] Company Strategy and Development Direction - The company is focused on advancing its lead therapeutic candidate, autologous cardiac cell therapy, and plans to share two-year data with regulatory authorities to align on pathways for making the therapy available [21][24] - Ongoing discussions with regulatory agencies aim to highlight the safety and efficacy of cardiac cell therapy, emphasizing the lack of long-term safety issues compared to traditional therapies [23][24] - The company is also progressing in other therapeutic programs, including the Cardi-AMP Cell Therapy and Chronic Myocardial Ischemia Trial [26] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism regarding the strength of the two-year data and its potential impact on future trials and regulatory discussions [43][70] - The company is preparing a submission package for the PMDA in Japan, with expectations for a consultation meeting soon [78][82] - Management acknowledged the need for continued engagement with regulatory authorities to ensure a smooth approval process [81] Other Important Information - The company has completed enrollment in the low-dose cohort of its cardi-allo-allogeneic mesenchymal stem cell therapy in ischemic heart failure [26] - The Helix biotherapeutic delivery platform is expected to enhance future commercialization and clinical development efficiency [31][32] Q&A Session Summary Question: Can you provide more details on PMDA discussions in Japan? - Management met with PMDA in November and is preparing to share two-year data, which looks promising for potential conditional approval in Japan [42][43] Question: Were there any subsequent therapies that could have impacted the data read? - All patients were on guideline-directed medical therapy, and no other medications were introduced during the trial [47][50] Question: What is the expected timeline for sharing two-year data with the FDA? - The company is compiling the data for submission and expects to have a meeting with the FDA soon, with a timeline potentially as short as three weeks [70][82] Question: How does the data from Heart Failure 1 inform Heart Failure 2 trials? - The primary endpoint structure remains the same, and the company aims to replicate the positive outcomes observed in the first trial [88] Question: What are the next steps regarding interactions with the PMDA? - The company is preparing a submission package and scheduling a consultation meeting with the PMDA, with expectations for a timeline of three to eight weeks [78][82]

Financial Data and Key Metrics Changes - Nuwellis generated $2.3 million in revenue for Q4 2024, a 9% decrease year-over-year due to a decline in U.S. console sales and international sales, offset by a 21% increase in consumables utilization [10][20] - Gross margin improved to 58.4% for Q4 2024 compared to 54.4% in the prior year quarter, driven by higher manufacturing volumes of consumables and lower fixed overhead manufacturing expenses [21] - Net loss attributable to common shareholders in Q4 was $1.5 million, or a loss of $0.44 per share, compared to a net loss of $7.9 million, or a loss of $54.48 per share for the same period in 2023 [24][25] Business Line Data and Key Metrics Changes - The Critical Care business, the largest customer category, saw a 35% year-over-year quarterly revenue growth, benefiting from higher console sales and consumable utilization [11][20] - Heart failure and pediatric customer categories experienced declines of 36% and 20% respectively due to lower console sales [12][20] Market Data and Key Metrics Changes - The company reported nine new account wins throughout 2024, indicating positive market penetration [9] - A favorable reimbursement change effective January 1, 2025, allows Nuwellis to enter the outpatient services market for Aquadex technology, with the facility reimbursement fee increasing nearly fourfold from $413 to $1,639 per day [14][15] Company Strategy and Development Direction - Nuwellis aims to build its body of clinical evidence to make Aquadex Ultrafiltration therapy a standard of care and integrate it into medical society guidelines [12] - The company is focused on driving market penetration of Aquadex Ultrafiltration therapy, leveraging clinical evidence and increased reimbursement rates in the outpatient setting [16] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism for 2025, highlighting the positive impact of new account wins and reimbursement changes on growth [9] - The recent publication in JACC: Heart Failure demonstrated a 60% reduction in heart failure events for patients treated with Aquadex compared to traditional IV diuretics, which is expected to support broader adoption of the technology [13][18] Other Important Information - The company had a voluntary recall of specific lots of blood circuit units, which resulted in a non-recurring expense of approximately $150,000 [22] - Total operating expenses decreased by approximately 25% compared to Q4 2023, reflecting savings from operational efficiency initiatives [24] Q&A Session Summary Question: Initial traction in the outpatient setting for Aquadex - Management noted that traction is beginning with several existing accounts needing to set up permanent outpatient facilities, with more activity expected in the coming month [29] Question: Number of Aquadex units sold in Q4 2024 and Q3 2024 - Three units were sold in Q4 2024, compared to 11 units in Q3 2024 [33][35] Question: Timing for reverse HF trial enrollment completion - Management indicated it is difficult to gauge the timing for enrollment completion [37] Question: Timing for the start of the Vivian clinical trial - Management provided a similar response, stating it is difficult to predict [39] Question: Changes in leadership and search for a new CEO - Management confirmed that a search firm has been hired and candidates are being evaluated, with no immediate need for major changes in direction [46]