Financial Data and Key Metrics Changes - The combined R&D and SG&A expenses for Q4 2024 totaled $3 million, down from $4.6 million in Q4 2023, reflecting a decrease in personnel and administrative expenses [49][50] - Cash operating expenses for 2025 are expected to be in the range of $18-19 million [50] Business Line Data and Key Metrics Changes - The NEPHRO CRRT study has been reduced in size from 166 patients to 70, maintaining a primary endpoint power of 90% [13][30] - The company has added three new clinical study sites, bringing the total to eight enrollment-ready sites, with plans to have 13 by mid-year [22][43] Market Data and Key Metrics Changes - The company has secured a private placement investment of up to $14.8 million, contingent on achieving certain milestones [9][48] - The financing is structured in three tranches, with the first tranche expected shortly in April [47] Company Strategy and Development Direction - The company is focused on completing the NEPHRO study by the end of 2025, with strategic changes to the study protocol and site selection to enhance enrollment [46][48] - The management believes that the clinical, regulatory, and commercial risks for the NEPHRO program are low due to the established safety and efficacy of the anticoagulant used [24] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in meeting the timeline for the NEPHRO study completion, citing improved site engagement and protocol changes [112][113] - The FDA's responsiveness and approval of protocol changes have been highlighted as key factors in the study's progress [14][24] Other Important Information - The company has identified an ideal site profile for the NEPHRO study, focusing on nephrologist-led sites and medical ICUs to improve patient enrollment [39][41] - The company is actively pursuing additional clinical sites to maximize enrollment potential [43] Q&A Session Summary Question: What were the original thoughts on the exclusion criteria for the NEPHRO study? - The original 48-hour restriction was likely based on concerns about patient recovery times, but it was determined that it had no impact on the primary endpoint [60][61] Question: Why have institutions decided not to use heparin? - Institutions cited the risks associated with heparin, including its long half-life and systemic anticoagulation effects, which increase bleeding risks in high-risk patients [70][72] Question: Is there a time limit tied to the milestones for the private placement? - There is no specific time limit for achieving the milestones related to patient enrollment [76] Question: Will there be a shift in primary investigators to nephrologists at existing sites? - Discussions are ongoing to potentially shift primary responsibilities to nephrologists at existing sites, and unproductive sites may be deactivated if they do not perform [91][92] Question: What gives confidence in having phase three data by the end of the year? - The company has already engaged with additional sites and believes that the enrollment of patients can be accelerated based on the new site profiles and engagement [112][113]

Financial Performance - The net loss from continuing operations for Q4 2024 was $1.9 million, compared to a net loss of $4.5 million in Q4 2023, reflecting improved financial performance[10] - The net loss attributable to common shareholders for Q4 2024 was $1.9 million, or $0.07 per share, compared to a net loss of $4.5 million, or $0.25 per share, in Q4 2023[10] - Talphera reported cash and investments of $8.9 million as of December 31, 2024, and announced a private placement financing of up to $14.8 million[10] - The company recognized no revenue for Q4 2024, consistent with Q4 2023, while total revenue for the year was $0 compared to $651,000 in 2023[18] Expenses and Cost Management - Combined R&D and SG&A expenses for Q4 2024 totaled $3.0 million, down from $4.6 million in Q4 2023, primarily due to reductions in personnel and administrative expenses[10] - Talphera expects cash operating expenses in 2025 to be between $18 million and $19 million, including costs related to the NEPHRO CRRT trial[7] - Research and development expenses for Q4 2024 were $1.323 billion, a decrease from $1.769 billion in Q4 2023, representing a decline of about 25.2%[21] - Selling, general and administrative expenses for Q4 2024 were $1.673 billion, down from $2.795 billion in Q4 2023, reflecting a decrease of approximately 40.2%[21] - Total operating expenses for Q4 2024 were $2.996 billion, a decrease from $4.564 billion in Q4 2023, indicating a decline of about 34.4%[21] - Non-GAAP operating expenses for the year ended December 31, 2024, were $14.263 billion, down from $15.830 billion in 2023, representing a decrease of approximately 9.9%[21] - Stock-based compensation expense for the year ended December 31, 2024, was $989 million, down from $1.710 billion in 2023, indicating a decrease of about 42.0%[21] - The company is focusing on cost reduction strategies, as evidenced by the significant decrease in both operating expenses and stock-based compensation[21] Assets and Liabilities - Cash, cash equivalents, and investments decreased to $8.863 billion in 2024 from $9.381 billion in 2023, representing a decline of approximately 5.5%[20] - Total assets decreased to $18.236 billion in 2024, down from $20.395 billion in 2023, reflecting a decrease of about 10.6%[20] - Total liabilities increased significantly to $10.235 billion in 2024, compared to $6.290 billion in 2023, marking an increase of approximately 62.5%[20] - Total stockholders' equity fell to $8.001 billion in 2024, down from $14.105 billion in 2023, indicating a decrease of around 43.4%[20] Clinical Trials and Product Development - The FDA approved a reduction in the NEPHRO CRRT study size from 166 to 70 patients, with a primary endpoint powered at 90%[4] - The company plans to complete the NEPHRO CRRT study by the end of 2025, supported by new site additions and increased enrollment potential[3] - Talphera's lead product candidate, Niyad™, is being studied as an anticoagulant and has received Breakthrough Device Designation from the FDA[11]

Core Insights - The FDA has approved a reduction in the NEPHRO CRRT study patient count from 166 to 70, which is expected to enhance the study's execution momentum [2][6] - Talphera anticipates completing the NEPHRO CRRT study by the end of 2025, supported by new site additions and financing [2][6] - The company reported a net loss of $1.9 million for Q4 2024, a significant improvement from a net loss of $4.5 million in Q4 2023 [4][17] Financial Highlights - As of December 31, 2024, Talphera had cash and investments totaling $8.9 million, with an additional private placement financing of up to $14.8 million announced [6][19] - Combined R&D and SG&A expenses for Q4 2024 were $3.0 million, down from $4.6 million in Q4 2023, primarily due to reduced personnel and administrative costs [4][20] - The net loss attributable to common shareholders for Q4 2024 was $1.9 million, or $0.07 per share, compared to a net loss of $4.5 million, or $0.25 per share, in Q4 2023 [4][17] Study and Product Development - The NEPHRO CRRT study is designed to evaluate the efficacy of Niyad in patients undergoing renal replacement therapy who cannot tolerate heparin [13] - The primary endpoint of the study is the mean post-filter activated clotting time using Niyad versus placebo over the first 24 hours [13] - Niyad has received Breakthrough Device Designation from the FDA, indicating its potential to address significant unmet needs in the CRRT market [10][12]

Core Viewpoint - The FDA has approved a reduction in the NEPHRO CRRT study size from 166 to 70 patients, which is expected to facilitate timely completion by the end of 2025, supported by a capital raise of up to $14.8 million through a private placement [1][2][11] Group 1: NEPHRO CRRT Study - The NEPHRO CRRT study will now enroll 70 adult patients undergoing renal replacement therapy, focusing on those who cannot tolerate heparin or are at risk for bleeding [11] - The primary endpoint of the study is the mean post-filter activated clotting time using Niyad versus placebo over the first 24 hours, with key secondary endpoints including filter lifespan and dialysis efficacy [11] Group 2: Financing and Capital - Talphera has entered into securities purchase agreements for a private placement led by Nantahala Capital and Rosalind Advisors, aiming to raise up to $14.8 million [1][3] - The first closing is expected to yield $4.925 million, with additional tranches contingent on patient enrollment milestones [3][4] - Cash and investments as of December 31, 2024, are projected to be $8.9 million, which, along with the financing proceeds, should support the completion of the NEPHRO CRRT study [1][2] Group 3: Company Overview - Talphera, Inc. is a specialty pharmaceutical company focused on developing innovative therapies for medically supervised settings, with its lead product candidate, Niyad™, currently under investigation [8][10] - Niyad™ has received Breakthrough Device Designation from the FDA and is being studied as an anticoagulant for the extracorporeal circuit [10]

Core Viewpoint - Talphera, Inc. is set to release its fourth quarter and full-year 2024 financial results on March 31, 2025, followed by a live webcast and conference call to discuss the results and provide a business update [1]. Group 1: Financial Results Announcement - The financial results will be released after market close on March 31, 2025 [1]. - A live webcast and conference call will take place at 4:30 p.m. Eastern Time/1:30 p.m. Pacific Standard Time [1]. Group 2: Webcast and Conference Call Details - The webcast can be accessed through the Investors section of Talphera's website, with a slide presentation included [2]. - A replay of the webcast will be available for 90 days following the event [2]. - Investors can participate in the conference call by dialing specific numbers for North American and international callers, with a conference ID provided [3]. Group 3: Company Overview - Talphera, Inc. focuses on developing and commercializing innovative therapies for medically supervised settings [4]. - The lead product candidate, Niyad™, is a lyophilized formulation of nafamostat, currently studied as an anticoagulant and has received Breakthrough Device Designation from the FDA [4].

Core Viewpoint - Talphera, Inc. is advancing its NEPHRO CRRT clinical study with FDA's agreement on protocol changes aimed at accelerating patient enrollment and reducing the number of patients required for the study [1][2][3] Group 1: FDA Interactions and Protocol Changes - The FDA has agreed to review a Prior Approval Supplement (PAS) for a reduction in the number of patients in the NEPHRO CRRT study, which is expected to be submitted within the coming week [1] - Two additional protocol changes have been approved by the FDA to broaden inclusion criteria, allowing enrollment of patients on continuous renal replacement therapy (CRRT) beyond 48 hours and heparin-tolerant patients at certain institutions [2] - The PAS review by the FDA will take up to 30 days, and the company is optimistic about completing the study by the end of the year [3] Group 2: Product and Study Details - Talphera's lead product candidate, Niyad™, is a lyophilized formulation of nafamostat, currently under investigation as an anticoagulant for the extracorporeal circuit and has received Breakthrough Device Designation from the FDA [4][6] - The NEPHRO CRRT study aims to enroll 166 adult patients undergoing renal replacement therapy who cannot tolerate heparin or are at risk for bleeding, with primary and secondary endpoints focused on clotting time and dialysis efficacy [7]

Financial Data and Key Metrics Changes - Cash operating expenses for Q3 2024 totaled $3.5 million, an increase from $3 million in the same period last year, attributed to the NEPHRO CRRT clinical study [20] - Year-to-date cash operating expenses reached $11.5 million, with full-year 2024 expenses expected to be in the range of $15 million to $17 million [21] - Cash and investments at the end of Q3 2024 amounted to $11.1 million, with an additional capital injection likely required before the completion of the NEPHRO study [21] Business Line Data and Key Metrics Changes - The NEPHRO CRRT study has onboarded five active clinical trial sites, with two additional sites expected to begin screening, totaling seven by the end of the year [7][8] - The primary endpoint of the NEPHRO trial is the mean activated clotting time measured over the first 24 hours, with patient participation lasting 72 hours [9] Market Data and Key Metrics Changes - The FDA has expanded the maximum number of trial sites from 10 to 14, indicating a proactive approach to enhance patient enrollment [15] - The company is focusing on high-volume CRRT sites with broader ICU populations to optimize patient recruitment [13] Company Strategy and Development Direction - The company is committed to improving enrollment rates at existing sites and onboarding new productive sites to expedite the NEPHRO trial [8][14] - There is a strong emphasis on leveraging breakthrough designation from the FDA to facilitate study enrollment and completion [18] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in nafamostat's potential clinical utility, citing a long track record of efficacy and safety in Japan and South Korea [17] - The company anticipates having more information on the clinical trial's progress early next year, indicating a positive outlook for future developments [16] Other Important Information - The company is consulting regulatory experts to implement potential changes to study design elements to facilitate enrollment [14] - Management highlighted the need for an alternative anticoagulant in CRRT, reinforcing the market opportunity for nafamostat [15] Q&A Session Summary Question: Can you walk through the optimization on the screening to drive enrollment? - Management discussed the need for improved site engagement and automated notifications to capture patients before CRRT begins, addressing previous enrollment challenges [26][27] Question: What percentage of patients are screened and successfully enrolled? - Management noted that screening percentages fluctuate by site, and feedback from physicians has been positive regarding patient experiences in the trial [40][41] Question: Will data from the NEPHRO study be available next year? - Management confirmed that the goal is to have data available next year, with a short timeline from study completion to PMA submission [44] Question: What measures are planned to accelerate enrollment? - Management mentioned ongoing evaluations of study design and the implementation of new site strategies to enhance patient identification and enrollment [46][47]

Financial Performance - Total revenue for the three months ended September 30, 2024, was $117,000, compared to $370,000 for the same period in 2023, representing a decrease of approximately 68.4%[13] - The net loss for the three months ended September 30, 2024, was $3,353,000, compared to a net loss of $1,357,000 for the same period in 2023, indicating a worsening of 146.5%[13] - Basic and diluted loss per share for continuing operations was $(0.13) for the three months ended September 30, 2024, compared to $(0.08) for the same period in 2023[13] - As of September 30, 2023, the company reported a net loss of $1,357,000, with total equity amounting to $18,307,000[15] - For the nine months ended September 30, 2023, the net loss was $13,880,000, with cash used in operating activities totaling $10,429,000[16] - The company recognized a net loss from discontinued operations of $8.098 million for the nine months ended September 30, 2023, with total revenues of $501,000 during the same period[47] Expenses and Costs - Research and development expenses for the nine months ended September 30, 2024, were $5,395,000, an increase of 42.8% from $3,777,000 for the same period in 2023[13] - Total operating costs and expenses for the three months ended September 30, 2024, were $3,749,000, compared to $3,426,000 for the same period in 2023, reflecting an increase of 9.4%[13] - The Company recorded total stock-based compensation expense of $234,000 for the three months ended September 30, 2024, compared to $378,000 for the same period in 2023[79] Equity and Liabilities - Total stockholders' equity decreased to $9,641,000 as of September 30, 2024, down from $14,105,000 as of December 31, 2023[10] - The accumulated deficit increased to $(455,360,000) as of September 30, 2024, compared to $(444,226,000) as of December 31, 2023[10] - The company reported total liabilities and stockholders' equity of $21,014,000 as of September 30, 2024, compared to $20,395,000 as of December 31, 2023[10] Cash and Financing Activities - The company had cash and cash equivalents of $11,117,000 at the end of the reporting period, down from $20,275,000 at the beginning of the period[16] - The company raised $8,924,000 from a private placement offering in July 2023, contributing to net cash provided by financing activities of $12,044,000 for the nine months ended September 30, 2023[16] - The Company entered into a private placement on January 17, 2024, resulting in aggregate gross proceeds of $6.0 million upfront, with an additional $10.0 million contingent upon positive clinical trial results for the NEPHRO CRRT study of Niyad[65] - The first tranche of the private placement closed on January 22, 2024, generating approximately $6.0 million for pre-funded warrants to purchase up to 7,792,208 shares of common stock[66] Product Development and Strategy - The company is focused on advancing the development of its lead product candidate, Niyad™, and aims to secure regulatory approval and commercialization[6] - The company is focused on developing Niyad™, a regional anticoagulant, and LTX-608, a nafamostat formulation, for various medical indications[18][21] - The company completed an asset acquisition agreement for the DSUVIA product on April 3, 2023, which included the transfer of certain assets and liabilities[20] Risks and Concerns - The company faces significant risks including market volatility, supply chain disruptions, and the ability to obtain necessary financing for ongoing operations[6] - The company has incurred recurring operating losses and negative cash flows since inception, raising concerns about its ability to continue as a going concern[23] - The Company may need to reduce its workforce or delay clinical trials if adequate funds are not available[25] Accounting and Financial Reporting - The Company is evaluating the impact of recently issued accounting standards but does not expect them to materially affect its consolidated financial statements[36] - Management's significant accounting estimates include fair value of warrants and impairment of long-lived assets, which could differ from actual results[28] - The effective interest rate for the liability related to the sale of future payments will be reassessed at each reporting date[33] Stock and Equity Compensation - The Company amended its 2020 Equity Incentive Plan to increase the number of authorized shares by 1,171,395, bringing the total to 3,161,395 shares[72] - The Company granted stock-based awards totaling 217,000 shares to a new employee as an inducement for employment in May 2024[73] - The Company amended its 2011 Employee Stock Purchase Plan to increase the number of authorized shares by 100,000, resulting in a total of 345,000 shares available for issuance[74] - As of September 30, 2024, the total stock options outstanding increased to 1,879,806, with a weighted average remaining contractual life of 7.7 years[81] Litigation - The Company believes ongoing litigation is without merit and intends to defend against it, but cannot estimate potential losses due to the uncertainty of litigation outcomes[64]

Financial Performance - Net loss from continuing operations for Q3 2024 was $3.4 million, compared to a net loss of $1.4 million in Q3 2023[7]. - Net loss attributable to common shareholders for Q3 2024 was $3.4 million, or $0.13 per share, compared to a net loss of $1.4 million, or $0.08 per share, in Q3 2023[8]. - Total operating costs and expenses for Q3 2024 were $3.7 million, compared to $3.4 million in Q3 2023[6]. - Total operating expenses for the three months ended September 2024 were $3,749,000, slightly up from $3,426,000, an increase of 9.4%[21]. - Non-GAAP operating expenses for the three months ended September 2024 were $3,515,000, compared to $3,048,000 for the same period in 2023, an increase of 15.3%[21]. - Total operating expenses for the nine months ended September 2024 were $12,256,000, slightly down from $12,976,000 for the same period in 2023, a decrease of 5.5%[21]. Cash and Investments - Cash and investments totaled $11.1 million as of September 30, 2024[5]. - Cash, cash equivalents, and investments increased to $11,117,000 from $9,381,000, representing a growth of 18.5%[20]. - Total assets rose to $21,014,000, up from $20,395,000, indicating an increase of 3.0%[20]. - Total liabilities increased significantly to $11,373,000 from $6,290,000, reflecting an increase of 80.5%[20]. - Total stockholders' equity decreased to $9,641,000 from $14,105,000, a decline of 31.7%[20]. Research and Development - Combined R&D and SG&A expenses for Q3 2024 were $3.7 million, up from $3.4 million in Q3 2023, primarily due to NEPHRO study costs[6]. - Research and development expenses for the three months ended September 2024 were $2,053,000, up 74.4% from $1,178,000 for the same period in 2023[21]. - The NEPHRO CRRT study aims to enroll 166 patients across up to 14 clinical sites in the U.S.[4]. - The first patient was enrolled in the NEPHRO CRRT study in August 2024[3]. - The study's primary endpoint is the mean post-filter activated clotting time for circuits infused with nafamostat compared to placebo over the first 24 hours[4]. - Talphera anticipates completing the NEPHRO study by the end of 2025 with improved enrollment rates[2]. Operating Expenses - Selling, general, and administrative expenses decreased to $1,696,000 from $2,248,000, a reduction of 24.5%[21]. - Stock-based compensation expense for the three months ended September 2024 was $234,000, down from $378,000, a decrease of 38.3%[21]. Regulatory Status - The company has received Breakthrough Device Designation status from the FDA for its lead product candidate, Niyad™[11].

Company Overview - Talphera, Inc. is a specialty pharmaceutical company focused on developing and commercializing innovative therapies for medically supervised settings [4] - The company's lead product candidate, Niyad™, is a lyophilized formulation of nafamostat, currently studied as an anticoagulant for the extracorporeal circuit and has received Breakthrough Device Designation from the FDA [4] - Talphera is also developing two pre-filled syringes in partnership with Aguettant: Fedsyra™, a pre-filled ephedrine syringe, and PFS-02, a pre-filled phenylephrine syringe [4] Financial Results Announcement - Talphera will release its third quarter 2024 financial results after market close on November 13, 2024 [1] - A live webcast and conference call will be held at 4:30 p.m. Eastern Time/1:30 p.m. Pacific Standard Time to discuss the results and provide a business update [1] Webcast and Conference Call Details - The webcast can be accessed through the Investors section of Talphera's website, and a replay will be available for 90 days following the event [2] - Investors can participate in the conference call by dialing 1-800-836-8184 for North American callers or 1-646-357-8785 for international callers, with a conference ID of 89949 [3]