Core Viewpoint - Talphera is focusing on the potential of nafamostat as an anticoagulant in continuous renal replacement therapy (CRRT), addressing an unmet need in the market [2]. Group 1: Business Update - The event includes a brief business update before transitioning to expert discussions on CRRT and anticoagulants [3]. Group 2: Expert Discussion - The discussion features Dr. Shakil Aslam, Talphera's Chief Medical Officer, and two principal investigators in the NEPHRO CRRT registrational study, emphasizing their expertise in CRRT [2]. Group 3: Future Outlook - The company acknowledges that forward-looking statements may be made during the call, which involve risks and uncertainties regarding operations and future results [3].

Financial Data and Key Metrics Changes - Talphera reported a cash and investments balance of $20.4 million as of December 31, 2025, which, along with remaining financing tranches, is expected to provide a runway through potential FDA approval of Niyad next year [5] - The company achieved gross proceeds of $4.1 million from the closing of the third tranche of financing triggered by reaching the 50% enrollment milestone in the Nephro CRRT study [4] Business Line Data and Key Metrics Changes - The Nephro CRRT study is progressing well, with the company reaching the 50% enrollment milestone [4] - The primary endpoint of the study is measured at 24 hours, indicating a quick turnaround of data is expected once patient enrollment is completed [5] Market Data and Key Metrics Changes - The incidence rates of acute kidney injury (AKI) severe enough to require dialysis, particularly continuous renal replacement therapy (CRRT), are increasing, indicating a growing market for Talphera's products [28] - The chronic dialysis population in the U.S. is stabilizing, while the ICU population requiring CRRT is growing, suggesting a shift in market dynamics [27] Company Strategy and Development Direction - Talphera aims to address the unmet need for anticoagulation in CRRT circuits with nafamostat, which is being studied in the Nephro CRRT registrational study [3] - The company expects to complete enrollment of the NEPHRO CRRT study later this year and file the PMA within about three months after study completion [5] Management's Comments on Operating Environment and Future Outlook - Management highlighted the increasing complexity of patients in ICUs and the corresponding rise in acute kidney injury cases, which is expected to dominate nephrology practice in the future [28] - The management expressed optimism about the potential for nafamostat to fill a significant gap in current anticoagulation options for CRRT [3] Other Important Information - The company is focused on continuous renal replacement therapy (CRRT), which is a critical treatment for patients in intensive care units [6] - There are significant challenges in managing anticoagulation during CRRT, with current options like heparin and citrate having limitations [43][55] Q&A Session Summary Question: What are the key differences between CRRT and intermittent hemodialysis? - CRRT is used for critically ill patients requiring gentle, continuous dialysis, while intermittent hemodialysis is for more stable patients [20][23] Question: What trends are being observed in the incidence rates of end-stage kidney disease versus acute kidney injury? - The chronic dialysis population is stabilizing, while acute kidney injury cases are increasing, particularly in ICU settings [27][28] Question: What are the implications of filter clotting in CRRT? - Clotting leads to interruptions in therapy, increased nursing workload, and potential blood loss, which can be detrimental to critically ill patients [48][51] Question: What anticoagulation strategies are being used? - Citrate is preferred in some institutions due to its efficacy, but it requires careful monitoring and can be complex to manage [57][134]

Financial Data and Key Metrics Changes - The company announced Q4 and full-year financial results, achieving a gross proceeds of $4.1 million from the third tranche of financing triggered by reaching the 50% enrollment milestone in the Nephro CRRT study [5][6]. - As of December 31, the company had cash and investments totaling $20.4 million, which, along with remaining tranches, is expected to provide a runway through a potential FDA approval of Niyad next year [6]. Business Line Data and Key Metrics Changes - The Nephro CRRT study is progressing well, with expectations to complete enrollment later this year and file the PMA within about three months after study completion [6]. Market Data and Key Metrics Changes - The incidence rates of acute kidney injury (AKI) severe enough to require dialysis, particularly continuous renal replacement therapy (CRRT), are increasing, driven by factors such as septic shock and the growing complexity of ICU patients [29][30][40]. Company Strategy and Development Direction - The company aims to address the unmet need for anticoagulation in CRRT circuits, with a focus on nafamostat as a potential solution [3][5]. - The management highlighted the importance of continuous renal replacement therapy in the ICU setting, emphasizing the need for effective anticoagulation strategies to prevent filter clotting [7][44]. Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the growth of the CRRT market, noting that the patient population requiring such therapies is expected to continue increasing due to the aging population and rising chronic kidney disease rates [29][33]. - The management acknowledged the challenges associated with current anticoagulation methods, particularly heparin, and the need for improved alternatives like citrate, despite its complexities [56][101]. Other Important Information - The company is actively involved in discussions about the complexities and challenges of using citrate as an anticoagulant, which has implications for nursing staff and patient safety [141][160]. - The management noted logistical challenges related to the storage and administration of citrate solutions, which can complicate treatment protocols [164][171]. Q&A Session Summary Question: What are the key differences between CRRT and intermittent hemodialysis? - CRRT is used for critically ill patients in the ICU, providing continuous and gentler dialysis, while intermittent hemodialysis is typically for more stable outpatient chronic dialysis patients [21][24]. Question: Are there any trends in the incidence rates of end-stage kidney disease versus acute kidney injury? - The chronic dialysis population is stabilizing, while the incidence of acute kidney injury is increasing, particularly in ICU settings [28][30]. Question: What anticoagulation strategies are being used? - The use of citrate is becoming more common, but it presents challenges in monitoring and administration, while heparin is often avoided due to its inefficacy and bleeding risks [56][101][128].

Financial Data and Key Metrics Changes - The company announced Q4 and full-year financial results, achieving a gross proceeds of $4.1 million from the third tranche of financing triggered by reaching the 50% enrollment milestone in the Nephro CRRT study [3][4] - As of December 31, the company had cash and investments totaling $20.4 million, which, along with remaining tranches, is expected to provide a runway through potential FDA approval of Niyad next year [4] Business Line Data and Key Metrics Changes - The Nephro CRRT study is progressing well, with expectations to complete enrollment later this year and file the PMA within about three months after study completion [4] Market Data and Key Metrics Changes - Continuous renal replacement therapy (CRRT) is increasingly recognized as a critical treatment modality for patients in intensive care units, with a growing incidence of acute kidney injury requiring such interventions [26][27] Company Strategy and Development Direction - The company is focused on addressing unmet needs in anticoagulation for CRRT, with management emphasizing the importance of effective anticoagulants to prevent filter clotting during treatment [5][6] - The management is aware of the complexities and challenges associated with current anticoagulation methods, such as heparin and citrate, and is exploring better options for patient safety and efficacy [8][9] Management's Comments on Operating Environment and Future Outlook - Management highlighted the increasing complexity of patients in ICUs and the rising incidence of acute kidney injury, suggesting that the demand for CRRT will continue to grow [27][30] - There is a recognition that the chronic dialysis population is stabilizing, while the acute kidney injury population is expanding, indicating a shift in treatment focus [25][28] Other Important Information - The company is actively engaging with key experts in the field to enhance understanding and management of CRRT, which is crucial for improving patient outcomes [2][6] Q&A Session Summary Question: What are the key differences between CRRT and intermittent hemodialysis? - CRRT is a continuous, gentle form of dialysis for critically ill patients, while intermittent hemodialysis is typically for more stable patients [20][22] Question: Are there any trends in the incidence rates of end-stage kidney disease versus acute kidney injury? - The chronic dialysis population is stabilizing, while the incidence of acute kidney injury is increasing, particularly in ICU settings [25][27] Question: What are the challenges associated with using citrate as an anticoagulant? - Citrate requires intensive monitoring and can lead to metabolic disturbances, making its use complex and burdensome for nursing staff [140][156] Question: What is the current status of heparin use in CRRT? - Heparin is still used but is not favored due to its unpredictability and systemic anticoagulation risks; citrate is preferred despite its complexities [101][123] Question: What is the ideal profile for an anticoagulant in CRRT? - An ideal anticoagulant would be effective, safe for high-risk patients, and remain confined to the circuit without systemic effects [210][218]

As filed with the Securities and Exchange Commission on March 26, 2024 Registration No. 333-276537 UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 Pre-effective Amendment No. 1 to FORM S-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 ENSYSCE BIOSCIENCES, INC. (Exact name of registrant as specified in its charter) (State or Other Jurisdiction of Incorporation or Organization) Delaware 2834 82-2755287 (Primary Standard Industrial Classification Code Number) (I.R.S. Employer ...

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As filed with the Securities and Exchange Commission on November 17, 2023 Registration No. 333-275456 UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 Pre-effective Amendment No. 1 to FORM S-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 ENSYSCE BIOSCIENCES, INC. (Exact name of registrant as specified in its charter) (State or Other Jurisdiction of Incorporation or Organization) (Primary Standard Industrial Delaware 2834 82-2755287 (I.R.S. Employer Identification Number) 79 ...

(State or Other Jurisdiction of Incorporation or Organization) As filed with the Securities and Exchange Commission on November 9, 2023 Registration No. 333-****** UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM S-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 ENSYSCE BIOSCIENCES, INC. (Exact name of registrant as specified in its charter) (Primary Standard Industrial Classification Code Number) Delaware 2834 82-2755287 (I.R.S. Employer Identification Number) 7946 Iva ...

ENSYSCE BIOSCIENCES, INC. (Exact name of registrant as specified in its charter) (State or Other Jurisdiction of Incorporation or Organization) (Primary Standard Industrial As filed with the Securities and Exchange Commission on May 9, 2023 Registration No. 333-271480 UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 Pre-effective Amendment No. 2 to FORM S-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 Delaware 2834 82-2755287 (I.R.S. Employer Identification Number) 7946 Iva ...

As filed with the Securities and Exchange Commission on May 8, 2023 Registration No. 333-271480 UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 Pre-effective Amendment No. 1 to FORM S-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 ENSYSCE BIOSCIENCES, INC. (Exact name of registrant as specified in its charter) (State or Other Jurisdiction of Incorporation or Organization) (Primary Standard Industrial Delaware 2834 82-2755287 (I.R.S. Employer Identification Number) 7946 Iva ...