Core Insights - Talphera, Inc. has achieved a significant milestone in its NEPHRO CRRT clinical trial by enrolling 17 out of the planned 70 patients, which is approximately 25% of the total enrollment target [1][2] - The company is on track to complete the study by the end of 2025, supported by an accelerated recruitment rate from new clinical sites [1][2] Enrollment Progress - The NEPHRO CRRT trial has seen an increase in enrollment, with 17 patients now participating, up from 15 just a week prior [2] - Over 90% of the enrolled patients are coming from newly targeted clinical sites, indicating a successful re-launch of the study [2] Study Design and Objectives - The NEPHRO CRRT Study is a prospective, double-blinded trial conducted in up to 14 U.S. hospital intensive care units, focusing on 70 adult patients who cannot tolerate heparin or are at risk for bleeding [3] - The primary endpoint 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 [3] Product Information - Niyad is a lyophilized formulation of nafamostat, a synthetic serine protease inhibitor with anticoagulant and anti-inflammatory properties, currently under investigation as an anticoagulant for extracorporeal circuits [4][5] - The product has received Breakthrough Device Designation from the FDA, highlighting its potential significance in medical applications [5] Company Overview - Talphera, Inc. specializes in developing and commercializing innovative therapies for medically supervised settings, with a focus on products like Niyad [5]

Financial Data and Key Metrics Changes - The company reduced its expected cash operating expense guidance for 2025 to a range of $16 million to $17 million, down from the previous range of $17 million to $19 million [20] - Cash operating expenses for 2025 totaled $3.7 million compared to $4.3 million for 2024, indicating a decrease primarily due to reductions in personnel and general administrative expenses [20][21] - The cash balance as of June 30, 2025, was $6.8 million, which includes proceeds from the first tranche of financing [21] Business Line Data and Key Metrics Changes - The enrollment rate for the Nephros study has more than doubled since May, with a strong acceleration observed in the last six weeks [5][12] - The company has shifted its focus to new clinical study sites, specifically targeting nephrologists as principal investigators, which has led to improved enrollment rates [7][12] Market Data and Key Metrics Changes - There is a growing interest from healthcare providers in Nafamostat due to ongoing shortages of heparin and citrate, which are commonly used anticoagulants [9][39] - The company is advancing a compassionate use IDE for Nafamostat, indicating a strong market potential for the product if approved [9][15] Company Strategy and Development Direction - The company is focused on completing the nephro CRRT registrational trial by the end of 2025, with a clear regulatory path and breakthrough designation from the FDA [17][19] - The strategy includes adding new clinical study sites with a focus on nephrology to enhance patient enrollment and engagement [12][56] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the low clinical, regulatory, and commercial risks associated with the Nafamostat program, citing its established track record in Japan and South Korea [17] - The management team is optimistic about the potential for Nafamostat to become the only FDA-approved regional anticoagulant for CRRT if approved [10][19] Other Important Information - The company is in discussions with multiple institutions regarding the compassionate use of Nafamostat for specific patient populations that do not respond well to existing anticoagulants [9][15] - The company has made significant changes to its clinical study design, including reducing the study size and adjusting the target profile of clinical sites [4][6] Q&A Session Summary Question: What is the expected enrollment acceleration to reach the 70 patient target by year-end? - Management indicated that the enrollment rates are significantly increasing with new sites, and they are confident in reaching the target based on current trends [25][26] Question: Is there an opportunity to leverage data from compassionate use for future publications? - Management confirmed that data collected from compassionate use patients will contribute to a larger safety dataset, which could be beneficial for future publications and commercial uptake [30][33] Question: What is the status of heparin and citrate shortages? - Management noted that heparin shortages are episodic and ongoing, while citrate shortages are also being reported, affecting supply predictability [38][39] Question: What are the main components driving down operating expenses? - Management expects operating expenses to increase in the second half of the year due to rising enrollment rates [43] Question: What gives confidence in the new site initiations? - Management highlighted improved vetting processes and historical data on site performance, indicating high confidence in having new sites operational by the end of the third quarter [50][56]

PART I. FINANCIAL INFORMATION Talphera's unaudited financial statements, management's analysis, market risk, and internal controls are presented [Item 1. Financial Statements](index=3&type=section&id=Item%201.%20Financial%20Statements) Talphera's unaudited condensed consolidated financial statements and notes detail financial position, operations, cash flows, and equity, highlighting liquidity and going concern [Condensed Consolidated Balance Sheets](index=6&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) This section presents the company's financial position, including assets, liabilities, and equity, as of specific reporting dates Condensed Consolidated Balance Sheet Highlights (in thousands) | Metric | June 30, 2025 | December 31, 2024 | | :-------------------------------- | :------------ | :------------------ | | Cash and cash equivalents | $6,791 | $8,863 | | Total current assets | $7,696 | $9,417 | | Total assets | $16,515 | $18,236 | | Total current liabilities | $2,630 | $2,647 | | Total liabilities | $9,888 | $10,235 | | Total stockholders' equity | $6,627 | $8,001 | - Common stock outstanding increased to **20,522,655 shares** as of June 30, 2025, from **17,029,469 shares** as of December 31, 2024[14](index=14&type=chunk) [Condensed Consolidated Statements of Operations](index=7&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) This section details the company's revenues, expenses, and net loss over specific reporting periods Condensed Consolidated Statements of Operations Highlights (in thousands, except per share data) | Metric | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :----------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Revenue | $— | $— | $27 | $— | | Research and development | $1,500 | $1,909 | $2,669 | $3,342 | | Selling, general and administrative | $2,193 | $2,361 | $3,967 | $5,165 | | Total operating costs and expenses | $3,693 | $4,270 | $6,636 | $8,507 | | Loss from operations | $(3,693) | $(4,270) | $(6,609) | $(8,507) | | Total other income, net | $204 | $443 | $454 | $726 | | Net loss | $(3,489) | $(3,827) | $(6,082) | $(7,781) | | Basic and diluted loss per share | $(0.10) | $(0.15) | $(0.20) | $(0.31) | [Condensed Consolidated Statements of Stockholders' Equity](index=8&type=section&id=Condensed%20Consolidated%20Statements%20of%20Stockholders%20Equity) This section outlines changes in the company's equity, including common stock, additional paid-in capital, and accumulated deficit Changes in Stockholders' Equity (in thousands) | Metric | Balance as of January 1, 2025 | Balance as of June 30, 2025 | | :----------------------------------- | :---------------------------- | :-------------------------- | | Common Stock (Shares) | 17,029,469 | 20,522,655 | | Common Stock (Amount) | $17 | $20 | | Additional Paid-in Capital | $465,214 | $469,919 | | Accumulated Deficit | $(457,230) | $(463,312) | | Total Stockholders' Equity | $8,001 | $6,627 | - Net proceeds from the issuance of common stock and pre-funded warrants in connection with equity financing for the six months ended June 30, 2025, amounted to **$4,354 thousand**[21](index=21&type=chunk) [Condensed Consolidated Statements of Cash Flows](index=9&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) This section summarizes the company's cash inflows and outflows from operating, investing, and financing activities Condensed Consolidated Statements of Cash Flows Highlights (in thousands) | Cash Flow Activity | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :-------------------------------- | :----------------------------- | :----------------------------- | | Net cash used in operating activities | $(6,418) | $(7,493) | | Net cash provided by investing activities | $— | $3,181 | | Net cash provided by financing activities | $4,346 | $12,014 | | Net change in cash and cash equivalents | $(2,072) | $7,702 | | Cash and cash equivalents—End of period | $6,791 | $13,423 | [Notes to Condensed Consolidated Financial Statements](index=10&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) These notes provide detailed disclosures on the company's organization, significant accounting policies, financial instrument valuations, discontinued operations, sale of future payments, legal commitments, equity transactions, stock-based compensation, net loss per share, and segment reporting [1. Organization and Summary of Significant Accounting Policies](index=10&type=section&id=1.%20Organization%20and%20Summary%20of%20Significant%20Accounting%20Policies) This note describes the company's business, product pipeline, and critical accounting policies, including its going concern status - Talphera, Inc. is a specialty pharmaceutical company focused on developing and commercializing innovative therapies for medically supervised settings[26](index=26&type=chunk)[78](index=78&type=chunk) - The company's product development portfolio includes Niyad™ (a regional anticoagulant for dialysis) and LTX-608 (a nafamostat formulation for direct IV infusion for indications like DIC, ARDS, acute pancreatitis, or as an anti-viral treatment)[26](index=26&type=chunk)[27](index=27&type=chunk)[78](index=78&type=chunk) - The company has incurred recurring operating losses and negative cash flows, raising **substantial doubt** about its ability to continue as a **going concern**, and expects to need **additional capital** within the next twelve months[28](index=28&type=chunk)[103](index=103&type=chunk) [2. Investments and Fair Value Measurement](index=12&type=section&id=2.%20Investments%20and%20Fair%20Value%20Measurement) This note details the company's cash, cash equivalents, and fair value measurements of financial instruments, particularly warrant liabilities Cash and Cash Equivalents (in thousands) as of June 30, 2025 | Category | Fair Value | | :-------------------------- | :--------- | | Cash | $615 | | Money market funds | $404 | | U.S. government agency securities | $5,772 | | **Total** | **$6,791** | - The warrant liability, a Level III measurement, was valued at **$759 thousand** as of June 30, 2025, reflecting a **gain** on change in fair value of **$302 thousand** for the six months ended June 30, 2025, compared to a **loss** of **$547 thousand** for the same period in 2024[42](index=42&type=chunk)[100](index=100&type=chunk) [3. Discontinued Operations](index=14&type=section&id=3.%20Discontinued%20Operations) This note provides financial information related to the company's discontinued operations and associated accrued liabilities Net Income from Discontinued Operations (in thousands) | Period | Net Income | | :----------------------------- | :--------- | | Six months ended June 30, 2025 | $73 | | Six months ended June 30, 2024 | $— | - Accrued liabilities for discontinued operations were **$650 thousand** as of June 30, 2025, down from **$723 thousand** as of December 31, 2024[46](index=46&type=chunk) [4. Sale of Future Payments](index=14&type=section&id=4.%20Sale%20of%20Future%20Payments) This note explains the accounting for the sale of future DSUVIA payments and its impact on other income - In January 2024, the company recognized **$1.2 million** in other income from the sale of future commercial DSUVIA payments to XOMA (US) LLC[48](index=48&type=chunk)[99](index=99&type=chunk) - Alora Pharmaceuticals, LLC discontinued DSUVIA sales efforts to non-DoD customers in October 2024, leading the company to estimate future payments under the Purchase Agreement will be less than proceeds, resulting in a **0% estimated effective interest rate** for the six months ended June 30, 2025[50](index=50&type=chunk) [5. Commitments and Contingencies](index=16&type=section&id=5.%20Commitments%20and%20Contingencies) This note discloses the company's legal proceedings, including securities class action and shareholder derivative complaints - A securities class action complaint, dismissed with prejudice on May 7, 2024, is currently under appeal by plaintiffs in the Ninth Circuit Court of Appeals[52](index=52&type=chunk)

[Company Overview and Recent Developments](index=1&type=section&id=Company%20Overview%20and%20Recent%20Developments) [Second Quarter 2025 Highlights & Corporate Update](index=1&type=section&id=Second%20Quarter%202025%20Highlights%20%26%20Corporate%20Update) Talphera announced its second quarter 2025 financial results and provided a corporate update, highlighting significant progress in the NEPHRO clinical study with accelerated patient enrollment and a strategic financing round to support ongoing operations - **15 patients** have been enrolled in the NEPHRO clinical study, which remains on track for completion by the end of **2025**, with a planned PMA submission in the **first quarter of 2026**[1](index=1&type=chunk)[3](index=3&type=chunk) - Enrollment momentum has accelerated in the last six weeks due to new target profile clinical sites and study protocol changes, with new sites enrolling **90% of patients** to date[2](index=2&type=chunk) - Talphera announced the closing of the first tranche of **$4.9 million** of a three-tranche financing for up to **$14.8 million**, led by existing investors Nantahala Capital and Rosalind Advisors[3](index=3&type=chunk) [About Talphera, Inc.](index=3&type=section&id=About%20Talphera%2C%20Inc.) Talphera is a specialty pharmaceutical company focused on developing and commercializing innovative therapies for use in medically supervised settings, with Niyad® (nafamostat) as its lead product candidate - Talphera, Inc. is a specialty pharmaceutical company focused on the development and commercialization of innovative therapies for use in medically supervised settings[9](index=9&type=chunk) - Talphera's lead product candidate, **Niyad®**, is a lyophilized formulation of nafamostat, currently being studied under an investigational device exemption (IDE) as an anticoagulant for the extracorporeal circuit[9](index=9&type=chunk) - **Niyad®** has received Breakthrough Device Designation status from the U.S. Food and Drug Administration (FDA)[9](index=9&type=chunk) [Clinical Development](index=1&type=section&id=Clinical%20Development) [NEPHRO CRRT Study Progress](index=1&type=section&id=NEPHRO%20CRRT%20Study%20Progress) The NEPHRO clinical study is progressing well, with accelerated patient enrollment and strategic expansion of clinical sites, supporting the projected completion by year-end 2025 and a subsequent PMA submission in Q1 2026 - **15 patients** have been enrolled in the NEPHRO clinical study, supporting the expected completion timeline by the end of **2025**[1](index=1&type=chunk)[3](index=3&type=chunk) - Enrollment momentum has increased, with new target profile clinical sites enrolling **90% of patients** to date[2](index=2&type=chunk) - Talphera expects to add **six new clinical sites** by the end of the **third quarter**, bringing the total number of sites up to **13**, including **nine** with the target profile[2](index=2&type=chunk)[3](index=3&type=chunk) - A planned PMA submission is anticipated in the **first quarter of 2026**, assuming enrollment and site activation trends continue[3](index=3&type=chunk) [About Niyad and Nafamostat](index=3&type=section&id=About%20Niyad%20and%20Nafamostat) Nafamostat is a broad-spectrum synthetic serine protease inhibitor with anticoagulant, anti-inflammatory, and potential anti-viral activities. Niyad® is its lyophilized formulation, currently undergoing a registrational study (NEPHRO CRRT) as an anticoagulant for extracorporeal circuits, and has received Breakthrough Device Designation - **Nafamostat** is a broad-spectrum, synthetic serine protease inhibitor with anticoagulant, anti-inflammatory and potential anti-viral activities[11](index=11&type=chunk) - **Niyad®** is a lyophilized formulation of nafamostat, currently being studied under an IDE as an anticoagulant for the extracorporeal circuit, and has received Breakthrough Device Designation Status from the FDA[11](index=11&type=chunk) - The registrational study of **Niyad®** is named the **NEPHRO CRRT** (Nafamostat Efficacy in Phase 3 Registrational Continuous Renal Replacement Therapy) study[11](index=11&type=chunk) - An ICD-10 procedural code, **XY0YX37**, has been issued for the extracorporeal introduction of nafamostat, and **LTX-608** is a proprietary nafamostat formulation for direct IV infusion with other potential therapeutic targets[11](index=11&type=chunk) [About the NEPHRO CRRT Study Design](index=3&type=section&id=About%20the%20NEPHRO%20CRRT%20Study%20Design) The NEPHRO CRRT Study is a prospective, double-blinded trial designed to enroll 70 adult patients undergoing renal replacement therapy who are at risk for bleeding or cannot tolerate heparin, evaluating Niyad®'s efficacy as an anticoagulant - The **NEPHRO CRRT Study** is designed as a prospective, double-blinded trial to be conducted at up to **14 U.S. hospital intensive care units**[12](index=12&type=chunk) - The study will enroll and evaluate **70 adult patients** undergoing renal replacement therapy, who cannot tolerate heparin or are at risk for bleeding[12](index=12&type=chunk) - The primary endpoint of the study is mean post-filter activated clotting time using **Niyad** versus placebo over the **first 24 hours**[12](index=12&type=chunk) - Key secondary endpoints include mean post-filter activated clotting time over **72 hours**, filter lifespan, number of filter changes over **72 hours**, number of transfusions over **72 hours**, and dialysis efficacy over the **first 24 hours**[12](index=12&type=chunk) [Financial Results](index=2&type=section&id=Financial%20Results) [Second Quarter 2025 Financial Information Overview](index=2&type=section&id=Second%20Quarter%202025%20Financial%20Information%20Overview) Talphera reported a reduced net loss for Q2 2025 compared to Q2 2024, primarily due to lower personnel and general administrative expenses, and provided updated, reduced guidance for 2025 cash operating expenses - Cash and cash equivalents balance was **$6.8 million** as of **June 30, 2025**[7](index=7&type=chunk) - Net loss from continuing operations for the **second quarter of 2025** was **$3.5 million**, compared to **$3.8 million** for the **second quarter of 2024**, largely due to reductions in personnel expense and change in fair value of warrant liability[7](index=7&type=chunk) - Net loss attributable to common shareholders for **Q2 2025** was **$3.5 million**, or **$0.10 per basic and diluted share**, compared to **$3.8 million**, or **$0.15 per basic and diluted share**, for **Q2 2024**[7](index=7&type=chunk) [2025 Expense Guidance](index=2&type=section&id=2025%20Expense%20Guidance) - Cash operating expenses (selling, general and administrative, and research and development expenses, excluding stock-based compensation) are expected to be in the range of **$16 million to $17 million** in **2025**[5](index=5&type=chunk) - This **2025** guidance is a reduction from the previously provided range of **$17 million to $19 million**[5](index=5&type=chunk) [Key Financial Results (Q2 2025 vs Q2 2024)](index=2&type=section&id=Key%20Financial%20Results%20(Q2%202025%20vs%20Q2%202024)) Combined R&D and SG&A Expenses (Q2 2025 vs Q2 2024) | Metric | Q2 2025 (in thousands) | Q2 2024 (in thousands) | Change (YoY) | | :----------------------------------- | :--------------------- | :--------------------- | :----------- | | Combined R&D and SG&A expenses | $3,700 | $4,300 | -$600 | | Excluding non-cash stock-based compensation | $3,500 | $4,000 | -$500 | | Net loss from continuing operations | $3,489 | $3,827 | -$338 | | Net loss attributable to common shareholders | $3,489 | $3,827 | -$338 | | Basic and diluted loss per share | $0.10 | $0.15 | -$0.05 | - The decrease in combined R&D and SG&A expenses in **Q2 2025** was primarily due to reductions in personnel expense and other general and administrative expenses[7](index=7&type=chunk) - The divestment of DSUVIA represents a discontinued operation; all historical operating results for the business are reflected within discontinued operations, with no DSUVIA related expenses in **Q2 2025** or **Q2 2024**[7](index=7&type=chunk) [Selected Financial Data Tables](index=5&type=section&id=Selected%20Financial%20Data%20Tables) The selected financial data tables provide a detailed breakdown of the company's statement of operations for the three and six months ended June 30, 2025 and 2024, balance sheet data as of June 30, 2025 and December 31, 2024, and a reconciliation of non-GAAP operating expenses [Statement of Operations Data](index=5&type=section&id=Statement%20of%20Operations%20Data) Statement of Operations Data (in thousands, except per share data) | Statement of Operations Data | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :------------------------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Revenue | $ - | $ - | $ 27 | $ - | | Research and development | 1,500 | 1,909 | 2,669 | 3,342 | | Selling, general and administrative | 2,193 | 2,361 | 3,967 | 5,165 | | Total operating costs and expenses | 3,693 | 4,270 | 6,636 | 8,507 | | Loss from operations | (3,693) | (4,270) | (6,609) | (8,507) | | Interest income and other income, net | 83 | 201 | 152 | 421 | | Gain on sale of future payments | - | - | - | 1,246 | | Gain (loss) on change in fair value of warrant liability | 121 | 455 | 302 | (547) | | Non-cash interest expense on liability related to sale of future payments | - | (213) | - | (394) | | Total other income, net | 204 | 443 | 454 | 726 | | Net loss from continuing operations | (3,489) | (3,827) | (6,155) | (7,781) | | Net income from discontinued operations | - | - | 73 | - | | Net loss | $ (3,489) | $ (3,827) | $ (6,082) | $ (7,781) | | Basic and diluted loss per share, continuing operations | $ (0.10) | $ (0.15) | $ (0.20) | $ (0.31) | | Basic and diluted loss per share, discontinued operations | $ - | $ - | $ 0.00 | $ - | | Basic and diluted loss per share | $ (0.10) | $ (0.15) | $ (0.20) | $ (0.31) | | Shares used in computing net loss per share, basic and diluted | 34,530 | 26,202 | 30,422 | 25,462 | Non-Cash Stock-Based Compensation Expense (in thousands) | Expense Type | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :----------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Research and development | $ 55 | $ 85 | $ 132 | $ 192 | | Selling, general and administrative | 111 | 138 | 230 | 333 | | Total | $ 166 | $ 223 | $ 362 | $ 525 | [Selected Balance Sheet Data](index=6&type=section&id=Selected%20Balance%20Sheet%20Data) Selected Balance Sheet Data (in thousands) | Metric | June 30, 2025 (Unaudited) | December 31, 2024 (Unaudited) | | :----------------------------------- | :-------------------------- | :---------------------------- | | Cash, cash equivalents and investments | $ 6,791 | $ 8,863 | | Total assets | 16,515 | 18,236 | | Total liabilities | 9,888 | 10,235 | | Total stockholders' equity | 6,627 | 8,001 | [Reconciliation of Non-GAAP Financial Measures](index=6&type=section&id=Reconciliation%20of%20Non-GAAP%20Financial%20Measures) Reconciliation of Non-GAAP Operating Expenses (in thousands) | Metric | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :----------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Operating expenses (GAAP): | | | | | | Research and development | $ 1,500 | $ 1,909 | $ 2,669 | $ 3,342 | | Selling, general and administrative | 2,193 | 2,361 | 3,967 | 5,165 | | Total operating expenses | 3,693 | 4,270 | 6,636 | 8,507 | | Less stock-based compensation expense | 166 | 223 | 362 | 525 | | Operating expenses (non-GAAP) | $ 3,527 | $ 4,047 | $ 6,274 | $ 7,982 | [Additional Information](index=2&type=section&id=Additional%20Information) [Conference Call and Webcast Information](index=2&type=section&id=Conference%20Call%20and%20Webcast%20Information) Talphera will host a conference call and webcast on August 14, 2025, to discuss the financial results and provide a business update, with details provided for participation and replay access - Talphera will hold a conference call and webcast on **Thursday, August 14, 2025**, at **4:30 p.m. Eastern Time/1:30 p.m. Pacific Time**[1](index=1&type=chunk)[6](index=6&type=chunk) - Investors can participate by dialing **1-800-836-8184** (North America) or **1-646-357-8785** (international), using conference ID **32530**[8](index=8&type=chunk) - A webcast, including a slide presentation, will be accessible via **www.talphera.com** and a replay will be available on the Talphera website for **90 days** following the event[8](index=8&type=chunk) [Forward-looking Statements](index=4&type=section&id=Forward-looking%20Statements) This press release contains forward-looking statements based on current expectations and assumptions, subject to risks and uncertainties that could cause actual results to differ materially, as detailed in the company's SEC filings - The press release contains forward-looking statements based upon Talphera's current expectations and assumptions, made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of **1995**[13](index=13&type=chunk) - These statements involve risks and uncertainties that could cause actual results to differ materially from those projected, anticipated or implied, including risks related to product development, regulatory approvals, commercialization, and liquidity[13](index=13&type=chunk) - Readers are cautioned not to place undue reliance on forward-looking statements, which speak only as of their original date, and are advised to consult Talphera's SEC reports for full details on risks[13](index=13&type=chunk) [Investor Contacts](index=4&type=section&id=Investor%20Contacts) Contact information for Talphera's Chief Financial Officer and LifeSci Advisors is provided for investor inquiries - Talphera Investor Contact: Raffi Asadorian, CFO, **650-216-3500**, investors@talphera.com[14](index=14&type=chunk) - LifeSci Advisors Contact: Kevin Gardner, **617-283-2856**, kgardner@lifesciadvisors.com[14](index=14&type=chunk)

Core Viewpoint - Talphera, Inc. is set to release its second quarter 2025 financial results on August 14, 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 for the second quarter of 2025 will be released after market close on August 14, 2025 [1]. - A live webcast and conference call will take place at 4:30 p.m. Eastern Time/1:30 p.m. Pacific Time on the same day [1]. Group 2: 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 post-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. is a specialty pharmaceutical company focused on developing 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 and has received Breakthrough Device Designation from the FDA [4].

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. Excluding non-cash stock-based compensation, the amounts were $2.7 million for Q1 2025 compared to $3.9 million for Q1 2024 [15][16] - The company reduced the lower end of its 2025 expected cash operating expense guidance to a range of $17 million to $19 million [15] 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 time to complete the study [4][5] - The company has added three new clinical study sites that are actively screening patients, with five more expected by mid-year [6][9] Market Data and Key Metrics Changes - There are ongoing shortages of citrate supply and potential supply chain issues with heparin, leading healthcare providers to inquire about the availability of Nefamostat [7] Company Strategy and Development Direction - The company is focused on completing the nephro study by the end of the year and has made significant progress in engaging new clinical study sites [5][10] - The company believes that NIAID, if approved, would fill a significant unmet medical need during renal replacement therapy, as it would be the only FDA-approved regional anticoagulant for use during continuous renal replacement therapy [8][14] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the low clinical, regulatory, and commercial risk elements for the nephro program due to the established track record of nafamostat and the clear regulatory path provided by the FDA [13][14] - The company anticipates that the changes made to the nephro CRRT study and the new sites will accelerate enrollment rates [16] Other Important Information - The company completed a PIPE financing structured in three equal tranches, with the first tranche received at the initial closing [16] - The cash balance as of March 31, 2025, was $5.4 million, or $9.8 million on a pro forma basis after the financing [16] 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 [18][19] Question: What are the challenges with legacy sites? - The legacy sites are still dependent on patient populations that may not align with the new broader criteria, which has limited their enrollment despite the changes [24][25]

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].

Financial Position - Cash and investments as of March 31, 2025, were $9.8 million, adjusted to include proceeds from the first tranche of private placement financing[1] - Cash and cash equivalents were $5.4 million as of March 31, 2025, down from $8.9 million at the end of 2024[19] - Total liabilities as of March 31, 2025, were $9.4 million, compared to $10.2 million at the end of 2024[19] Clinical Development - The company activated three new clinical study sites in 2025, with five additional sites expected by mid-year, totaling 13 sites[2] - The FDA approved a reduction in the NEPHRO CRRT clinical study from 166 patients to 70, with a primary endpoint powered at 90%[3] Financing Activities - Talphera secured financing of up to $14.8 million, with the first tranche of $4.4 million closing on April 2, 2025[4] Operating Expenses - Cash operating expenses for 2025 are expected to be between $17 million and $19 million, including costs for the NEPHRO CRRT trial[6] - Combined R&D and SG&A expenses for Q1 2025 totaled $2.9 million, down from $4.2 million in Q1 2024[8] Net Loss - The net loss from continuing operations for Q1 2025 was $2.7 million, compared to a net loss of $4.0 million in Q1 2024[8] - Net loss attributable to common shareholders for Q1 2025 was $2.6 million, or $0.10 per share, compared to a net loss of $4.0 million, or $0.16 per share, in Q1 2024[8]

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].