Financial Data and Key Metrics Changes - The cash operating expenses for Q1 2025 totaled $2.9 million, a decrease from $4.2 million in Q1 2024, indicating a reduction in personnel and general administrative expenses [17][18] - The company has adjusted its 2025 expected cash operating expense guidance to a range of $17 million to $19 million [17] Business Line Data and Key Metrics Changes - The nephro CRRT trial has seen a reduction in study size from 166 patients to 70 patients, which is expected to shorten the study completion time [4][5] - The company has added three new clinical study sites that are actively screening patients, with five more expected by mid-year [6][12] Market Data and Key Metrics Changes - There is an ongoing inquiry from healthcare providers regarding the availability of Nefamostat due to shortages of citrate and potential supply chain issues with heparin [7] Company Strategy and Development Direction - The company is focused on completing the nephro study by the end of 2025 and believes that the new site engagement will significantly contribute to study enrollment [11][15] - The company is exploring a compassionate use IDE for Nefamostat, responding to requests from institutions for patients who do not respond well to current anticoagulants [13] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the low clinical, regulatory, and commercial risks associated with the nephro program, citing a strong track record of nafamostat's efficacy and safety [15] - The company anticipates that the expanded enrollment criteria will lead to increased activity at both legacy and new sites, although immediate results from legacy sites have not yet materialized [24][30] Other Important Information - The company completed a PIPE financing structured in three tranches, with the first tranche received and the remaining tranches contingent on patient enrollment milestones [19] Q&A Session Summary Question: Has the broader enrollment criteria started to translate into increased enrollment? - Management noted that while there has been increased activity at the sites due to broader criteria, it has not yet translated into new patients from legacy sites [24][25] Question: What are the challenges faced by legacy sites in enrolling patients? - The legacy sites are primarily dependent on surgical ICUs or cardiothoracic ICUs, which limits their patient pool despite the expanded criteria [29]

Financial Performance - Total revenue for the three months ended March 31, 2025, was $27,000, compared to $0 for the same period in 2024, indicating a significant increase[18]. - Operating costs and expenses for the three months ended March 31, 2025, were $2,943,000, down 30.5% from $4,237,000 in the same period in 2024[18]. - Net loss for the three months ended March 31, 2025, was $2,593,000, an improvement from a net loss of $3,954,000 in the same period in 2024, representing a 34.4% reduction in losses[18]. - The accumulated deficit increased to $459,823,000 as of March 31, 2025, from $457,230,000 at the end of 2024, indicating ongoing financial challenges[15]. - The net loss for the three months ended March 31, 2025, was $2.6 million, compared to a net loss of $4.0 million for the same period in 2024, indicating a 35% improvement in losses year-over-year[80]. - For the three months ended March 31, 2025, net cash used in operating activities was $3.5 million, reflecting a net loss of $2.6 million[107]. Cash Flow and Liquidity - Cash and cash equivalents decreased to $5,388,000 as of March 31, 2025, from $8,863,000 at the end of 2024, reflecting a cash outflow of $3,475,000 during the quarter[23]. - As of March 31, 2025, the total cash and cash equivalents amounted to $5.388 million, a decrease from $8.863 million as of December 31, 2024, representing a decline of approximately 39.5%[42]. - The company expects to incur significant losses in 2025 and may require additional capital to fund operations before the twelve-month anniversary of the filing date of this report[97][99]. - The company anticipates needing additional capital to fund operations for at least the next twelve months[111]. - Current capital is not expected to be sufficient to fund operations for the next twelve months, raising doubts about the company's ability to continue as a going concern[127]. Shareholder and Equity Information - The company reported a total of 26,268,209 shares used in computing net loss per share for the three months ended March 31, 2025, compared to 24,721,964 shares for the same period in 2024[18]. - The Company issued 3,405,118 shares of common stock at a price of $0.586 per share, generating approximately $4.9 million in gross proceeds from the first closing of the 2025 Private Placement[69]. - The second and third closings of the 2025 Private Placement are contingent upon the enrollment of at least 17 and 35 patients in the Niyad NEPHRO CRRT study, respectively[70]. - As of September 30, 2024, stockholders' equity was reported at $9.6 million, which is below Nasdaq's compliance requirement[104]. - The company expects that if the 2025 Private Placement had closed on March 31, 2025, stockholders' equity would have been adjusted to $10.0 million[104]. Research and Development - The company is focused on developing Niyad™ and LTX-608, with Niyad™ receiving Breakthrough Device Designation status from the FDA[28]. - Research and development expenses for the three months ended March 31, 2025, were $1.169 million, an 18% decrease from $1.433 million in 2024, primarily due to a reduction in employee compensation and related expenses[89]. - The company has entered into an agreement with the FDA to reduce the size of the Niyad registrational study to 70 patients from 166, which may expedite the regulatory review process[77]. - The company is developing Niyad™, which has received Breakthrough Device Designation from the FDA, and expects to submit a PMA application for commercialization in the U.S.[156]. Operational Challenges - Talphera, Inc. has incurred recurring operating losses and negative cash flows since inception, raising substantial doubt about its ability to continue as a going concern[30]. - The company has incurred significant net losses since inception and expects to continue incurring losses in 2025 and beyond, raising doubts about its ability to continue as a going concern[123]. - The company may face delisting from Nasdaq if it cannot regain compliance with continued listing requirements[121]. - The company relies on third-party manufacturers and suppliers, which poses risks to the development of its product candidates[122]. - The company may face significant delays in clinical trials due to challenges in patient enrollment, which could increase development costs and negatively impact the company's valuation[150]. Legal and Regulatory Risks - The company believes ongoing litigation is without merit and intends to vigorously defend against it, although it cannot estimate potential losses from these actions[56]. - The FDA's approval process for the company's product candidates is time-consuming and may be subject to unexpected delays, which could adversely affect the company's financial condition[155]. - The company may face claims of patent infringement from competitors, which could hinder its ability to commercialize products[212]. - Business operations are subject to healthcare laws, with potential penalties for non-compliance impacting financial results[190]. Market and Competitive Environment - The company faces intense competition in the biotechnology and pharmaceutical industries, which may hinder the commercial potential of its products[161]. - Future sales of DSUVIA to the Department of Defense (DoD) are unpredictable and may not meet expectations due to external factors beyond the company's control[137]. - Coverage and adequate reimbursement for the company's product candidates may not be available, impacting profitability and market acceptance[163]. - Legislative and regulatory changes in the healthcare system may negatively affect the reimbursement landscape for the company's products[166]. Intellectual Property and Product Liability - The company is pursuing a number of U.S. patent applications and foreign national applications for its product candidates, but there is no guarantee these will result in issued patents[205]. - The company relies on patents and other intellectual property protections, but third parties may challenge these patents, impacting business operations[208]. - Current product liability insurance may not be sufficient to cover potential claims, and exclusions in the policy could lead to significant financial exposure[203]. - The company faces risks related to product liability claims, which could result in substantial liabilities and damage to its business reputation[202].

Exhibit 99.1 Talphera Announces First Quarter 2025 Financial Results and Provides Corporate Update Cash and investments at March 31, 2025, as adjusted to include the proceeds from the first tranche of the private placement financing which closed on April 2, 2025, were $9.8 million Three new clinical study sites activated and screening patients thus far in 2025, with five additional sites expected by mid-year, for a total of 13 Conference call and webcast to be held Wednesday, May 14, 2025 at 4:30 pm ET SAN ...

Financial Data and Key Metrics Changes - The combined R&D and SG&A expenses for Q4 2024 totaled $3 million, a decrease from $4.6 million in Q4 2023 [49] - Excluding non-cash, stock-based compensation, these amounts were $2.8 million for Q4 2024, compared to $4.3 million for Q4 2023 [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 [22][29] - The most productive current site has about 20 CRRT patients per month, while new sites are expected to have higher volumes [42][101] Market Data and Key Metrics Changes - The company anticipates a private placement investment of up to $14.8 million, contingent on achieving certain milestones [9] - The financing is structured in three equal tranches of $4.925 million, with the first tranche expected shortly [47] Company Strategy and Development Direction - The company is focused on completing the NEPHRO study by the end of 2025, with a strategic emphasis on reducing operating expenses [46] - The FDA has approved changes to the NEPHRO study protocol, which are expected to enhance enrollment speed and site efficiency [15][28] - The company is actively pursuing additional clinical study sites to meet its enrollment goals [43] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the timely development of NIAID and the planned submission of a PMA in Q1 of the following year [8] - The FDA's responsiveness has been highlighted as a key benefit of NIAID's breakthrough designation [14] - Management believes that clinical, regulatory, and commercial risks for the NEPHRO program are low due to extensive prior use of the product in other markets [24] Other Important Information - The company has identified an ideal clinical site profile based on ICU type and nephrologist involvement, which is expected to improve enrollment rates [39][41] - The company has experienced a much shorter activation time for new sites, with the most recent site taking less than four months to activate [42] Q&A Session Summary Question: What were the original thoughts on the movement to exclude certain patients in the previous year? - The original protocol likely excluded patients based on concerns about clinical endpoints related to time on CRRT, which was deemed irrelevant for the current study [60][62] Question: Why have institutions decided not to use heparin? - Institutions cited 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 tied to the milestones for patient enrollment [76] Question: Are there plans to shift PIs to nephrologists at existing sites? - Discussions are ongoing to shift primary responsibilities to nephrologists or broaden patient populations at existing sites [91][92] Question: What gives confidence that phase three data can be achieved 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]

Acquisition and Partnerships - The company acquired Lowell Therapeutics, Inc. for approximately $32.5 million, with up to $26.0 million in contingent consideration based on regulatory and sales milestones[25]. - The divestment of DSUVIA to Alora Pharmaceuticals in April 2023 includes royalties and sales-based milestones, while the company continues to market DSUVIA to the Department of Defense[43]. - The company has entered into an agreement with XOMA to sell rights to payments related to DSUVIA sales, providing funding for Niyad's development[44]. Product Development and Regulatory Approvals - Niyad™ has received an Investigational Device Exemption (IDE) and Breakthrough Device Designation from the FDA, with an ongoing registrational trial[26]. - The NEPHRO CRRT Study aims to enroll 70 adult patients and evaluate the efficacy of Niyad compared to placebo, focusing on mean post-filter activated clotting time[28]. - LTX-608 is being explored for indications including antiviral treatment and acute respiratory distress syndrome (ARDS), with initial studies showing potential benefits in COVID patients[29]. - The company is focusing on the registrational trial for Niyad while deprioritizing the development of pre-filled syringe product candidates due to recent FDA approvals of competing products[36]. - Niyad, a nafamostat product, is classified as a Class III medical device and is undergoing the PMA application process, which is generally more costly and time-consuming than the 510(k) process[64]. - The FDA has 180 days to review a filed PMA application, although the review often takes significantly longer, typically between one and three years[67][68]. - The Breakthrough Devices Program allows for expedited review of devices that provide significant advantages over existing treatments, but does not change the standards for approval[71]. - Post-approval requirements include conducting Phase 4 clinical trials to gain additional experience and ensuring compliance with cGMP requirements[61]. - The FDA may withdraw product approval if compliance with regulatory standards is not maintained, which could lead to severe consequences including product recalls[63]. - Manufacturers must establish validated systems to ensure products meet specifications and regulatory standards, and test each product batch prior to release[62]. - The FDA may require post-approval studies or surveillance to monitor the safety and effectiveness of devices after market release[70]. - The approval process for an NDA is lengthy, and the FDA may issue a Complete Response Letter if the submission does not meet approval criteria[59]. Financial Performance and Concerns - The company has not yet generated significant product revenue and anticipates continued losses in the future[17]. - There is substantial doubt regarding the company's ability to continue as a going concern without raising additional capital[17]. - The market price of the company's common stock has historically been highly volatile, which may affect investor confidence and capital raising efforts[19]. - The company faces significant penalties for violations of health regulatory laws, which could adversely affect operations and financial results[88]. - Sales of product candidates depend on third-party payer coverage and reimbursement, which is increasingly challenging due to cost containment efforts[89]. - Legislative changes, such as the Affordable Care Act and the Inflation Reduction Act, may impact the company's ability to commercialize products profitably[94]. - The company anticipates ongoing pressure to provide larger discounts or rebates to maintain acceptable reimbursement levels[89]. - The pricing of prescription drugs in foreign markets is subject to government control, which may affect profitability[91]. - Future healthcare reforms could limit or eliminate spending on development projects, affecting profitability[93]. - The company may need to conduct expensive pharmacoeconomic studies to demonstrate cost-effectiveness for product approval[89]. Compliance and Legal Matters - Compliance with federal and state healthcare laws, including the Anti-Kickback Statute, is critical to avoid legal scrutiny and potential penalties[78]. - The company is subject to stringent FDA regulations, including quality assurance procedures and medical device reporting regulations[79]. - The company is subject to ongoing legal challenges regarding the Medicare Drug Price Negotiation Program[97]. - There is increasing legislative interest in drug pricing practices, including the Medicare Drug Price Negotiation Program, which began in fiscal year 2023[97]. - The company may face adverse impacts from potential future healthcare reforms that could limit product pricing and reimbursement[98]. Intellectual Property and Market Potential - The company has filed an international patent application for Niyad's use as an anticoagulant, which could provide six years of data exclusivity upon FDA approval[27]. - The company is seeking patent protection for its product candidates, with recent filings expected to extend patent coverage into 2045[47]. - The peak sales potential for Niyad could exceed $200 million annually in the U.S., based on an addressable population of 500,000 patients undergoing CRRT and 350,000 patients undergoing IHD, representing a total market opportunity of $4.075 billion[32]. - Niyad would be the first FDA-approved product for regional anticoagulation in the extracorporeal circuit, targeting the 57% of the market currently using citrate or no anticoagulant[34]. Operational and Employee Matters - The company relies on third-party manufacturers and suppliers for its product candidates, which may pose risks to development timelines[17]. - The company relies on contract manufacturers for the production of Niyad, ensuring a backup manufacturer to avoid supply chain risks[41]. - As of December 31, 2024, the company employed 13 full-time employees, with approximately 85% based in San Mateo, CA[99]. - The company is committed to pay equity and conducts annual pay equity analyses[99]. - The company offers competitive salaries, stock options, and comprehensive benefits to foster employee ownership and development[100]. - There are no collective bargaining agreements in place, and the company maintains a good relationship with its employees[101]. Company Background - The company was incorporated as SuRx, Inc. in 2005 and changed its name to Talphera, Inc. in January 2024[102]. - The company files annual and quarterly reports with the SEC, making them available on its website[102]. - The company is classified as a smaller reporting company and is not required to provide certain financial disclosures[321].

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]

The U.S. Food and Drug Administration (FDA) agreed to reduce the number of patients in the NEPHRO CRRT study from 166 to 70 patients, of which 6 patients are already enrolled Talphera believes the NEPHRO CRRT study should be completed by the end of 2025 Existing investors, Nantahala Capital and Rosalind Advisors led the capital commitment priced at-the-market as defined by Nasdaq rules $4.925 million in gross proceeds at first closing with the potential to receive an additional $9.85 million across two $4.9 ...

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].