Disseminated Intravascular Coagulation

First Global Phase 3 Trial Showing Substantial Survival Advantage Over Chemotherapy, for Patients With Progression On or After Platinum-Based Chemotherapy THOUSAND OAKS, Calif., April 11, 2025 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced that the global Phase 3 DeLLphi-304 clinical trial evaluating IMDELLTRA® (tarlatamab-dlle) as a treatment for patients with small cell lung cancer (SCLC) who progressed on or after a single line of platinum-based chemotherapy met its primary endpoint at a planned interim analysis. IMDELLTRA demonstrated statistically significant and clinically meaningful improvement in overall survival (OS) compared to local standard-of-care (SOC) chemotherapy. "Small cell lung cancer is one of the most aggressive malignancies, with a high unmet need for more effective therapies.1 The topline results from DeLLphi-304 demonstrate overwhelming clinical benefit for people living with this devastating disease and affirm IMDELLTRA as standard of care," said Jay Bradner, M.D., executive vice president, Research and Development, at Amgen. "We look forward to sharing these results with the scientific community and health authorities as we continue our efforts to bring IMDELLTRA to patients worldwide." The safety profile for IMDELLTRA was consistent with its known profile. Detailed data from DeLLphi-304 will be presented at an upcoming medical congress. DeLLphi-304 is a global Phase 3 randomized controlled open-label clinical trial evaluating the efficacy and safety of IMDELLTRA as a treatment for patients with SCLC who progressed on or after a single line of platinum-based chemotherapy.2 Patients were randomized to receive either IMDELLTRA or local SOC chemotherapy (topotecan in all countries except Japan; lurbinectedin in the U.S., Canada, Australia, Singapore, Korea; and amrubicin in Japan).2,3 The primary outcome measure of the trial is OS.2 About IMDELLTRA® (tarlatamab-dlle) IMDELLTRA is a first-in-class immunotherapy engineered by Amgen researchers that binds to both DLL3 on tumor cells and CD3 on T cells, activating T cells to kill DLL3-expressing SCLC cells. This results in the formation of a cytolytic synapse with lysis of the cancer cell.4,5 DLL3 is a protein that is expressed on the surface of SCLC cells in ~85-96% of patients with SCLC, but is minimally expressed on healthy cells, making it an exciting target.6,7 IMDELLTRA® (tarlatamab-dlle) U.S. Indication IMDELLTRA® (tarlatamab-dlle) is indicated for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). About Small Cell Lung Cancer (SCLC) SCLC is one of the most aggressive and devastating solid tumor malignancies, with a 5-10% five-year relative survival rate across all stages combined.1 SCLC comprises about 15% of the more than 2.4 million patients diagnosed with lung cancer worldwide each year.8-10 Despite initial high response rates to first-line platinum-based chemotherapy, most patients quickly relapse within months and require subsequent treatment options.9 About Tarlatamab Clinical Trials Amgen's robust tarlatamab development program includes the DeLLphi clinical trials, which evaluate tarlatamab as both a monotherapy and in combination regimens in earlier lines of SCLC. Tarlatamab is being investigated in multiple studies including DeLLphi-303, a Phase 1b study investigating tarlatamab in combination with standard of care therapies in first-line ES-SCLC; DeLLphi-304, a randomized Phase 3 trial comparing tarlatamab monotherapy with standard of care chemotherapy in second-line treatment of SCLC; DeLLphi-305, a randomized Phase 3 trial comparing tarlatamab in combination with durvalumab versus durvalumab alone as first-line maintenance treatment in ES-SCLC; DeLLphi-306, a randomized placebo-controlled Phase 3 trial of tarlatamab following concurrent chemoradiotherapy in limited-stage SCLC; DeLLphi-308, a Phase 1b study evaluating subcutaneous tarlatamab in second line or later ES-SCLC; and DeLLphi-309, a Phase 2 study evaluating alternative intravenous dosing regimens with tarlatamab in second-line ES-SCLC.11 For more information, please visit . About Amgen Amgen discovers, develops, manufactures and delivers innovative medicines to help millions of patients in their fight against some of the world's toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what's known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases. In 2024, Amgen was named one of the "World's Most Innovative Companies" by Fast Company and one of "America's Best Large Employers" by Forbes, among other external recognitions. Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average®, and it is also part of the Nasdaq-100 Index®, which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization. For more information, visit Amgen.com and follow Amgen on X, LinkedIn, Instagram, YouTube and Threads. IMDELLTRA® (tarlatamab-dlle) Important Safety Information WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving IMDELLTRA®. Initiate treatment with IMDELLTRA® using the step-up dosing schedule to reduce the incidence and severity of CRS. Withhold IMDELLTRA® until CRS resolves or permanently discontinue based on severity. Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), including serious or life-threatening reactions, can occur in patients receiving IMDELLTRA®. Monitor patients for signs and symptoms of neurologic toxicity, including ICANS, during treatment and treat promptly. Withhold IMDELLTRA® until ICANS resolves or permanently discontinue based on severity. WARNINGS AND PRECAUTIONS Cytokine Release Syndrome (CRS): IMDELLTRA® can cause CRS including serious or life-threatening reactions. In the pooled safety population, CRS occurred in 55% of patients who received IMDELLTRA®, including 34% Grade 1, 19% Grade 2, 1.1% Grade 3 and 0.5% Grade 4. Recurrent CRS occurred in 24% of patients, including 18% Grade 1 and 6% Grade 2. Most events (43%) of CRS occurred after the first dose, with 29% of patients experiencing any grade CRS after the second dose and 9% of patients experiencing CRS following the third dose or later. Following the Day 1, Day 8, and Day 15 infusions, 16%, 4.3% and 2.1% of patients experienced ≥ Grade 2 CRS, respectively. The median time to onset of all grade CRS from most recent dose of IMDELLTRA® was 13.5 hours (range: 1 to 268 hours). The median time to onset of ≥ Grade 2 CRS from most recent dose of IMDELLTRA® was 14.6 hours (range: 2 to 566 hours). Clinical signs and symptoms of CRS included pyrexia, hypotension, fatigue, tachycardia, headache, hypoxia, nausea, and vomiting. Potentially life-threatening complications of CRS may include cardiac dysfunction, acute respiratory distress syndrome, neurologic toxicity, renal and/or hepatic failure, and disseminated intravascular coagulation (DIC). Administer IMDELLTRA® following the recommended step-up dosing and administer concomitant medications before and after Cycle 1 IMDELLTRA® infusions as described in Table 3 of the Prescribing Information (PI) to reduce the risk of CRS. Administer IMDELLTRA® in an appropriate health care facility equipped to monitor and manage CRS. Ensure patients are well hydrated prior to administration of IMDELLTRA®. Closely monitor patients for signs and symptoms of CRS during treatment with IMDELLTRA®. At the first sign of CRS, immediately discontinue IMDELLTRA® infusion, evaluate the patient for hospitalization and institute supportive care based on severity. Withhold or permanently discontinue IMDELLTRA® based on severity. Counsel patients to seek medical attention should signs or symptoms of CRS occur. Neurologic Toxicity, Including ICANS: IMDELLTRA® can cause serious or life-threatening neurologic toxicity, including ICANS. In the pooled safety population, neurologic toxicity, including ICANS, occurred in 47% of patients who received IMDELLTRA®, including 10% Grade 3. The most frequent neurologic toxicities were headache (14%), peripheral neuropathy (7%), dizziness (7%), insomnia (6%), muscular weakness (3.7%), delirium (2.1%), syncope (1.6%), and neurotoxicity (1.1%). ICANS occurred in 9% of IMDELLTRA®-treated patients. Recurrent ICANS occurred in 1.6% of patients. Most patients experienced ICANS following Cycle 2 Day 1 (24%). Following Day 1, Day 8, and Day 15 infusions, 0.5%, 0.5% and 3.7% of patients experienced ≥ Grade 2 ICANS, respectively. The median time to onset of ICANS from the first dose of IMDELLTRATM was 29.5 days (range: 1 to 154 days). ICANS can occur several weeks following administration of IMDELLTRATM. The median time to resolution of ICANS was 33 days (range: 1 to 93 days). The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Clinical signs and symptoms of ICANS may include but are not limited to confusional state, depressed level of consciousness, disorientation, somnolence, lethargy, and bradyphrenia. Patients receiving IMDELLTRA® are at risk of neurologic adverse reactions and ICANS resulting in depressed level of consciousness. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, in the event of any neurologic symptoms until they resolve. Closely monitor patients for signs and symptoms of neurologic toxicity and ICANS during treatment. At the first sign of ICANS, immediately evaluate the patient and provide supportive therapy based on severity. Withhold IMDELLTRA® or permanently discontinue based on severity. Cytopenias: IMDELLTRA® can cause cytopenias including neutropenia, thrombocytopenia, and anemia. In the pooled safety population, decreased neutrophils occurred in 12% including 6% Grade 3 or 4 of IMDELLTRA®-treated patients. The median time to onset for Grade 3 or 4 neutropenia was 29.5 days (range: 2 to 213). Decreased platelets occurred in 33% including 3.2% Grade 3 or 4. The median time to onset for Grade 3 or 4 decreased platelets was 50 days (range: 3 to 420). Decreased hemoglobin occurred in 58% including 5% Grade 3 or 4. Febrile neutropenia occurred in 0.5% of patients treated with IMDELLTRA®. Monitor patients for signs and symptoms of cytopenias. Perform complete blood counts prior to treatment with IMDELLTRA®, before each dose, and as clinically indicated. Based on the severity of cytopenias, temporarily withhold, or permanently discontinue IMDELLTRA®. Infections: IMDELLTRA® can cause serious infections, including life-threatening and fatal infections. In the pooled safety population, infections, including opportunistic infections, occurred in 41% of patients who received IMDELLTRA®. Grade 3 or 4 infections occurred in 13% of patients. The most frequent infections were COVID-19 (9%, majority during the COVID-19 pandemic), urinary tract infection (10%), pneumonia (9%), respiratory tract infection (3.2%), and candida infection (3.2%). Monitor patients for signs and symptoms of infection prior to and during treatment with IMDELLTRA® and treat as clinically indicated. Withhold or permanently discontinue IMDELLTRA® based on severity. Hepatotoxicity: IMDELLTRA® can cause hepatotoxicity. In the pooled safety population, elevated ALT occurred in 42%, with Grade 3 or 4 ALT elevation occurring in 2.1%. Elevated AST occurred in 44% of patients, with Grade 3 or 4 AST elevation occurring in 3.2%. Elevated bilirubin occurred in 15% of patients; Grade 3 or 4 total bilirubin elevations occurred in 1.6% of patients. Liver enzyme elevation can occur with or without concurrent CRS. Monitor liver enzymes and bilirubin prior to treatment with IMDELLTRA®, before each dose, and as clinically indicated. Withhold IMDELLTRA® or permanently discontinue based on severity. Hypersensitivity: IMDELLTRA® can cause severe hypersensitivity reactions. Clinical signs and symptoms of hypersensitivity may include, but are not limited to, rash and bronchospasm. Monitor patients for signs and symptoms of hypersensitivity during treatment with IMDELLTRA® and manage as clinically indicated. Withhold or consider permanent discontinuation of IMDELLTRA® based on severity. Embryo-Fetal Toxicity: Based on its mechanism of action, IMDELLTRA® may cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with IMDELLTRA® and for 2 months after the last dose. ADVERSE REACTIONS The most common (> 20%) adverse reactions were CRS (55%), fatigue (51%), pyrexia (36%), dysgeusia (36%), decreased appetite (34%), musculoskeletal pain (30%), constipation (30%), anemia (27%) and nausea (22%). The most common (≥ 2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes (57%), decreased sodium (16%), increased uric acid (10%), decreased total neutrophils (6%), decreased hemoglobin (5%), increased activated partial thromboplastin time (5%), decreased potassium (5%), increased aspartate aminotransferase (3.2%), decreased white blood cells (3.8%), decreased platelets (3.2%), and increased alanine aminotransferase (2.1%). Serious adverse reactions occurred in 58% of patients. Serious adverse reactions in > 3% of patients included CRS (24%), pneumonia (6%), pyrexia (3.7%), and hyponatremia (3.6%). Fatal adverse reactions occurred in 2.7% of patients including pneumonia (0.5%), aspiration (0.5%), pulmonary embolism (0.5%), respiratory acidosis (0.5%), and respiratory failure (0.5%). DOSAGE AND ADMINISTRATION: Important Dosing Information Administer IMDELLTRA® as an intravenous infusion over one hour. Administer IMDELLTRA® according to the step-up dosing schedule in the IMDELLTRA® PI (Table 1) to reduce the incidence and severity of CRS. For Cycle 1, administer recommended concomitant medications before and after Cycle 1 IMDELLTRA® infusions to reduce the risk of CRS reactions as described in the PI (Table 3). IMDELLTRA® should only be administered by a qualified healthcare professional with appropriate medical support to manage severe reactions such as CRS and neurologic toxicity including ICANS. Due to the risk of CRS and neurologic toxicity, including ICANS, monitor patients from the start of the IMDELLTRA® infusion for 22 to 24 hours on Cycle 1 Day 1 and Cycle 1 Day 8 in an appropriate healthcare setting. Recommend that patients remain within 1 hour of an appropriate healthcare setting for a total of 48 hours from start of the infusion with IMDELLTRA® following Cycle 1 Day 1 and Cycle 1 Day 8 doses, accompanied by a caregiver. Prior to administration of IMDELLTRA® evaluate complete blood count, liver enzymes, and bilirubin before each dose, and as clinically indicated. Ensure patients are well hydrated prior to administration of IMDELLTRA®. Please see IMDELLTRA® full Prescribing Information , including BOXED WARNINGS. Amgen Forward-Looking Statements This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including any statements on the outcome, benefits and synergies of collaborations, or potential collaborations, with any other company (including BeiGene, Ltd. or Kyowa Kirin Co., Ltd.), the performance of Otezla® (apremilast) , our acquisitions of ChemoCentryx, Inc., or Horizon Therapeutics plc (including the prospective performance and outlook of Horizon's business, performance and opportunities, and any potential strategic benefits, synergies or opportunities expected as a result of such acquisition), as well as estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes, effects of pandemics or other widespread health problems on our business, outcomes, progress, and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen, including our most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise. No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future. Even when clinical trials are successful, regulatory authorities may question the sufficiency for approval of the trial endpoints we have selected. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify safety, side effects or manufacturing problems with our products, including our devices, after they are on the market. Our results may be affected by our ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments involving current and future products, sales growth of recently launched products, competition from other products including biosimilars, difficulties or delays in manufacturing our products and global economic conditions, including those resulting from geopolitical relations or government actions. In addition, sales of our products are affected by pricing pressure, political and public scrutiny and reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment. Furthermore, our research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. Our business may be impacted by government investigations, litigation and product liability claims. In addition, our business may be impacted by the adoption of new tax legislation or exposure to additional tax liabilities. Further, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors, or we may fail to prevail in present and future intellectual property litigation. We perform a substantial amount of our commercial manufacturing activities at a few key facilities, including in Puerto Rico, and also depend on third parties for a portion of our manufacturing activities, and limits on supply may constrain sales of certain of our current products and product candidate development. An outbreak of disease or similar public health threat and the public and governmental effort to mitigate against the spread of such disease, could have a significant adverse effect on the supply of materials for our manufacturing activities, the distribution of our products, the commercialization of our product candidates, and our clinical trial operations, and any such events may have a material adverse effect on our product development, product sales, business and results of operations. We rely on collaborations with third parties for the development of some of our product candidates and for the commercialization and sales of some of our commercial products. In addition, we compete with other companies with respect to many of our marketed products as well as for the discovery and development of new products. Further, some raw materials, medical devices and component parts for our products are supplied by sole third-party suppliers. Certain of our distributors, customers and payers have substantial purchasing leverage in their dealings with us. The discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations. Our efforts to collaborate with or acquire other companies, products or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful. There can be no guarantee that we will be able to realize any of the strategic benefits, synergies or opportunities arising from the Horizon acquisition, and such benefits, synergies or opportunities may take longer to realize than expected. We may not be able to successfully integrate Horizon, and such integration may take longer, be more difficult or cost more than expected. A breakdown, cyberattack or information security breach of our information technology systems could compromise the confidentiality, integrity and availability of our systems and our data. Our stock price is volatile and may be affected by a number of events. Our business and operations may be negatively affected by the failure, or perceived failure, of achieving our sustainability objectives. The effects of global climate change and related natural disasters could negatively affect our business and operations. Global economic conditions may magnify certain risks that affect our business. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock. We may not be able to access the capital and credit markets on terms that are favorable to us, or at all. The scientific information discussed in this news release related to our product candidates is preliminary and investigative. Such product candidates are not approved by the U.S. Food and Drug Administration, and no conclusions can or should be drawn regarding the safety or effectiveness of the product candidates. Further, any scientific information discussed in this news release relating to new indications for our products is preliminary and investigative and is not part of the labeling approved by the U.S. Food and Drug Administration for the products. The products are not approved for the investigational use(s) discussed in this news release, and no conclusions can or should be drawn regarding the safety or effectiveness of the products for these uses. CONTACT: Amgen, Thousand Oaks Elissa Snook, 609-251-1407 (media) Justin Claeys, 805-313-9775 (investors) REFERENCES: PDQ® Adult Treatment Editorial Board. PDQ Small Cell Lung Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated June 27, 2024. Available at: . Accessed March 25, 2025. DeLLphi-304 Clinical Trial Listing. Available at: . Accessed March 24, 2025. Paz-Ares, et al. JCO. 41, TPS8611-TPS8611(2023). DOI:10.1200/JCO.2023.41.16_suppl.TPS8611 Giffin MJ, Cooke K, Lobenhofer EK, et al. AMG 757, a Half-Life Extended, DLL3-Targeted Bispecific T-Cell Engager, Shows High Potency and Sensitivity in Preclinical Models of Small-Cell Lung Cancer. Clin Cancer Res. 2021;27:1526-1537. Baeuerle PA, Kufer P, Bargou R. BiTE: Teaching antibodies to engage T-cells for cancer therapy. Curr Opin Mol Ther. 2009;11:22-30. Ahn MJ, Cho BC, Felip E, et al. Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer. N Engl J Med. 2023;389:2063-2075. Rojo F, Corassa M, Mavroudis D, et al. International real-world study of DLL3 expression in patients with small cell lung cancer. Lung Cancer. 2020;147:237-243. World Health Organization. Lung. 2022. Available at: . Accessed on March 24, 2025. Oronsky B, Abrouk N, Caroen S, et al. A 2022 Update on Extensive Stage Small-Cell Lung Cancer (SCLC). J Cancer. 2022;13:2945-2953. Sabari JK, Lok BH, Laird JH, et al. Unravelling the biology of SCLC: implications for therapy. Nat Rev Clin Oncol. 2017;14:549-561. Clinical Trials. Tarlatamab Clinical Trial Listings. . Accessed March 25, 2025. SOURCE Amgen WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

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 $4.925 million tranches upon achieving certain patient enrollment milestones Cash and investments at December 31, 2024 of $8.9 million, together with the expected proceeds from the financing of up to $14.8 million should provide capital through targeted completion of the NEPHRO CRRT study by the end of 2025 SAN MATEO, Calif., March 31, 2025 /PRNewswire/ -- Talphera, Inc. (Nasdaq: TLPH), (Talphera), a specialty pharmaceutical company focused on the development and commercialization of innovative therapies for use in medically supervised settings, today announced its agreement with the FDA to reduce the size of the NEPHRO CRRT study to 70 patients from the 166 previously included in the study protocol. The Company also announced it has entered into securities purchase agreements with certain institutional investors and a member of management for the sale and issuance of shares of common stock and pre-funded warrants in lieu of shares to purchase common stock in a three-tranche private placement for potential gross proceeds of up to $14.8 million. "We are pleased that the FDA agreed with our assessment to reduce the study size to 70 patients, which still keeps the study's primary endpoint powered at 90%," stated Vince Angotti, Talphera CEO. "This change, along with the other protocol changes to the study inclusion criteria and the addition of new sites with higher enrollment potential will support a timely completion of the study, which we are targeting by the end of the year. We are also thankful for the continued support from our existing investors, Nantahala and Rosalind, which led the private placement financing. The additional capital should support our objective of completing the study by the end of the year as we look forward to submitting our PMA early next year and a potential approval in the second half of 2026." The Private Placement The private placement is led by Nantahala Capital and Rosalind Advisors, and includes a member of management, and has the potential to raise gross proceeds of up to $14.8 million, which amount includes (i) $4.925 million in the first closing (which is expected to occur on April 2, 2025), (ii) $4.925 million in a second closing upon the enrollment of at least 17 patients in the Company's NEPHRO CCRT study (the "Second Milestone"), and a minimum stock price of at least $0.7325 per share for five consecutive days following a public announcement of the achievement of the Second Milestone, and (iii) $4.925 million in a third closing upon the enrollment of at least 35 patients (the "Third Milestone"), and a minimum stock price of at least $0.7325 per share for five consecutive days following a public announcement of the achievement of the Third Milestone. In the first closing, Talphera will issue 3,405,118 shares of common stock and 4,999,316 pre-funded warrants, at a price of $0.586 per share and $0.585 per pre-funded warrant, respectively. The pre-funded warrants will have an exercise price of $0.001 per share. In each of the second and third closings upon achievement of the respective milestones and if closing conditions are met, Talphera expects to issue an additional 3,405,118 shares of common stock and 4,999,316 pre-funded warrants, at a price of $0.586 per share and $0.585 per pre-funded warrant, respectively. The offer and sale of the securities described above are being offered and sold in a private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Act"), and Regulation D promulgated thereunder, and have not been registered under the Act, or applicable state securities laws. Accordingly, such securities may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Act and such applicable state securities laws. The Company has agreed to file a registration statement under the Act with the Securities and Exchange Commission (the "SEC"), covering the resale of the shares of common stock to be issued in the private placement and the shares of common stock underlying the pre-funded warrants no later than 45 days following the closing date, and to use reasonable best efforts to have the registration statement declared effective as promptly as practical thereafter, and in any event no later than 90 days following the closing date in the event of a "full review" by the SEC. This press release does not constitute an offer to sell or the solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any state or other jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or other jurisdiction. About Talphera, Inc. Talphera, Inc. is a specialty pharmaceutical company focused on the development and commercialization of innovative therapies for use in medically supervised settings. Talphera' s lead product candidate, Niyad™ is a lyophilized formulation of nafamostat and is currently being studied under an investigational device exemption (IDE) as an anticoagulant for the extracorporeal circuit, and has received Breakthrough Device Designation status from the U.S. Food and Drug Administration (FDA). This release is intended for investors only. For additional information about Talphera, please visit www.talphera.com. About Nafamostat Nafamostat is a broad spectrum, synthetic serine protease inhibitor with anticoagulant, anti-inflammatory and potential anti-viral activities. Niyad™ is a lyophilized formulation of nafamostat and is currently being studied under an IDE, as an anticoagulant for the extracorporeal circuit, and has received Breakthrough Device Designation Status from the FDA. Talphera's registrational study of Niyad™ is named the NEPHRO CRRT (Nafamostat Efficacy in Phase 3 Registrational Continuous Renal Replacement Therapy) study. An ICD-10 procedural code, XY0YX37, has been issued for the extracorporeal introduction of nafamostat. The ICD-10 code is a specific/billable code that can be used to indicate a procedure. LTX-608 is a proprietary nafamostat formulation for direct IV infusion that may be investigated and developed for the treatment of acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC), acute pancreatitis or as an anti-viral treatment, amongst other potential targets. About the NEPHRO CRRT Study The NEPHRO CRRT Study, which has received central IRB approval, is designed as a prospective, double-blinded trial to be conducted at up to 14 U.S. hospital intensive care units. The study will enroll and evaluate 70 adult patients undergoing renal replacement therapy, who cannot tolerate heparin or are at risk for bleeding. The primary endpoint of the study is mean post-filter activated clotting time using Niyad versus placebo over the first 24 hours. Key secondary endpoints include the 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 (based on urea concentration) over the first 24 hours. Forward-looking Statements This press release contains forward-looking statements based upon Talphera's current expectations. These and any other forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking terminology such as "potential," "potentially," "believe," "expect," "anticipate," "may," "will," "if," "enable," "should," "seek," "approximately," "intends," "intended," "plans," "planned," "planning," "targeted," "estimates," "sufficient," "benefits," or the negative of these words or other comparable terminology, and include Talphera's statements regarding and include Talphera's statements regarding a potential completion of the NEPHRO CRRT study by the end of 2025; Talphera's expectation that the committed capital from the financing, upon completion of certain milestones and meeting certain closing conditions, should provide sufficient capital to fund the completion of the study expected by the end of 2025, with an expected PMA application submitted in early 2026 and a potential approval in the second half of 2026; and Talphera's ability to successfully meet the enrollment goals and minimum stock price to achieve the Second Milestone and Third Milestone. The discussion of strategy, plans or intentions may also include forward-looking statements, which are predictions, projections and other statements about future events that are based on current expectations and assumptions. These forward-looking statements involve risks and uncertainties that could cause actual results to differ materially from those projected, anticipated or implied by such statements, including: (i) risks relating to Talphera's product development activities and ongoing commercial business operations; (ii) risks related to the ability of Talphera and its business partners to implement development plans, launch plans, forecasts and other business expectations; (iii) risks related to unexpected variations in market growth and demand for Talphera 's commercial and developmental products and technologies; (iv) risks related to Talphera 's liquidity and its ability to maintain capital resources sufficient to conduct the required clinical studies; (v) Talphera 's ability to retain its listing on the Nasdaq exchange; and (vi) risks relating to Talphera's ability to obtain regulatory approvals for its developmental product candidates. Although it is not possible to predict or identify all such risks and uncertainties, they may include, but are not limited to, those described under the caption "Risk Factors" and elsewhere in Talphera 's annual, quarterly and current reports (i.e., Form 10-K, Form 10-Q and Form 8-K) as filed or furnished with the SEC and any subsequent public filings. You are cautioned not to place undue reliance on any such forward-looking statements, which speak only as of the date such statements were first made. To the degree financial information is included in this press release, it is in summary form only and must be considered in the context of the full details provided in Talphera's most recent annual, quarterly or current report as filed or furnished with the SEC. Talphera's SEC reports are available at www.talphera.com under the "Investors" tab. Except to the extent required by law, Talphera undertakes no obligation to publicly release the result of any revisions to these forward-looking statements to reflect new information, events or circumstances after the date hereof, or to reflect the occurrence of unanticipated events. View original content to download multimedia:https://www.prnewswire.com/news-releases/talphera-announces-agreement-with-the-fda-to-reduce-the-nephro-crrt-study-size-to-70-patients-from-166-and-a-private-placement-financing-priced-at-the-market-of-up-to-14-8-million-302415309.html SOURCE Talphera, Inc. Investor Contacts: Talphera, Raffi Asadorian, CFO, 650-216-3500, investors@talphera.com; LifeSci Advisors, Kevin Gardner, 617-283-2856, kgardner@lifesciadvisors.com

SOUTH SAN FRANCISCO, Calif.--( BUSINESS WIRE )--Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that a detailed analysis of its Phase III REGENCY trial of Gazyva ® (obinutuzumab) in people with active lupus nephritis (LN) was published in the New England Journal of Medicine . The trial demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of complete renal response (CRR), showing that 46.4% of people treated with Gazyva plus standard therapy (mycophenolate mofetil and glucocorticoids) achieved CRR at 76 weeks compared with 33.1% of people treated with standard therapy alone (adjusted difference 13.4%, 95% CI, 2.0%-24.8%; p=0.0232). This was accompanied by clinically meaningful improvements in complement levels and reductions in anti-dsDNA, markers of disease activity and inflammation. Data were presented at the World Congress of Nephrology (WCN) 2025 and are being shared with health authorities, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency. “The fact that nearly half of lupus nephritis patients achieved a complete renal response, together with clinically meaningful benefits observed consistently across subgroups, indicates superior disease control with Gazyva compared to standard treatment alone,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “Lupus nephritis disproportionately affects younger women, mostly women of color, often leading to end-stage kidney disease. Our goal is to address this urgent need by providing a more effective treatment option.” “The positive REGENCY study results confirmed the findings of an earlier trial that administration of obinutuzumab, a therapy which targets B cells, benefited patients with lupus nephritis more than standard treatment alone,” said Dr. Richard Furie, the Marilyn and Barry Rubenstein Chair in Rheumatology and Chief of the Division of Rheumatology at Northwell Health. “It is also gratifying to see that patients who received obinutuzumab were not only more likely to achieve the desired outcome but were able to taper corticosteroids at the same time.” Gazyva’s safety profile was consistent with the well-characterized profile observed in its hematology-oncology indications. Key secondary endpoints showed that at week 76, patients who received Gazyva plus standard therapy were more likely to achieve CRR, with a successful reduction of corticosteroid use than standard therapy alone. In addition, a higher proportion of patients also showed improvement in proteinuric response when treated with Gazyva plus standard therapy versus standard therapy alone. These endpoints are important indicators for achieving better disease control in lupus nephritis. As seen in pre-specified subgroup analyses, a benefit in CRR with Gazyva over standard therapy alone was consistent across all subgroups of patients including indicators of more active lupus nephritis, Class IV lupus nephritis, concomitant Class V disease, higher baseline proteinuria levels, and/or greater serologic activity. Further results for key secondary endpoints can be found in the table below and additional post hoc analysis is ongoing. Key secondary endpoints Obinutuzumab (n=135) Response % (95% CI) Placebo (n=136) Response % (95% CI) Treatment Difference (95% CI) P value CRR with prednisone taper (prednisone ≤7.5 mg/day Week 64 through Week 76) 42.7 (34.3, 51.1) 30.9 (23.1, 38.7) 11.9 (0.6, 23.2) 0.0421 Proteinuric response at Week 76 (UPCR <0.8 g/g) 55.5 (47.1, 64.0) 41.9 (33.6, 50.2) 13.7 (2.0, 25.4) 0.0227 Change in eGFR from baseline, adjusted mean 2.31 (2.71) -1.54 (2.71) 3.84 (-1.83, 9.51) 0.1842 Death or renal-related events through Week 76 18.9 (12.1, 25.6) 35.6 (27.5, 43.8) -16.83 (-27.4, -6.2) 0.0026* ORR at Week 50 59.1 (50.8, 67.4) 50.7 (42.2, 59.2) 8.4 (-3.4, 20.1) 0.1670 Change in FACIT-F from baseline, adjusted mean 1.8 (1.2) 3.1 (1.2) -1.4 (-3.9, 1.2) 0.2991 * Statistical significance cannot be claimed as endpoints earlier in the hierarchy were not met Lupus nephritis is a potentially life-threatening manifestation of an autoimmune disease that affects approximately 1.7 million people worldwide, predominantly women, mostly of color and childbearing age. Despite current treatment options, up to a third of people will develop end-stage kidney disease within 10 years, where dialysis or transplant are the only available options and the risk of mortality is high. Gazyva is the only anti-CD20 monoclonal antibody to demonstrate a CRR benefit in a randomized phase III study in lupus nephritis. Based on data from the Phase II NOBILITY study, Gazyva was granted Breakthrough Therapy Designation by the U.S. FDA in 2019. In addition to REGENCY, Gazyva is being investigated in children and adolescents with lupus nephritis, people with membranous nephropathy, childhood-onset idiopathic nephrotic syndrome and systemic lupus erythematosus (SLE), an autoimmune disease that commonly affects the kidneys and can lead to lupus nephritis. About Gazyva in Kidney Diseases Gazyva ® (obinutuzumab) is a Type II engineered humanized monoclonal antibody designed to attach to CD20, a protein found on certain types of B cells. In lupus nephritis, disease-causing B cells drive persistent inflammation that damages the kidneys. We can target an underlying cause of lupus nephritis to help gain better control of the disease by depleting disease-causing B cells with Gazyva, aiming to protect the kidneys from further damage and potentially prevent or delay progression to end-stage kidney disease. Gazyva is already approved in 100 countries for various types of lymphoma. In the United States, Gazyva is part of a collaboration between Genentech and Biogen. About the REGENCY Study REGENCY [ NCT04221477 ] is a Phase III, randomized, double-blind, placebo-controlled, multicenter study investigating the efficacy and safety of Gazyva ® (obinutuzumab) plus standard therapy (mycophenolate mofetil and glucocorticoids) in people with active/chronic International Society of Nephrology/Renal Pathology Society 2003 proliferative Class III or IV lupus nephritis, with or without Class V. The study enrolled 271 people, who were randomized 1:1 to receive either biannual intravenous dosing of Gazyva plus standard therapy or placebo plus standard therapy. REGENCY was designed based on robust Phase II data and conducted during the COVID-19 pandemic. The study population was representative of the real-world population of people with lupus nephritis. The primary endpoint was the proportion of people who achieved complete renal response (CRR) at 76 weeks. Key secondary endpoints included the proportion of people who achieved CRR at week 76 with successful reduction of corticosteroid use (prednisone taper); the proportion who achieved proteinuric response at 76 weeks; mean change in estimated glomerular filtration rate at 76 weeks; death or renal related events through week 76 and overall renal response at 50 weeks. Safety and tolerability were also assessed. About Lupus Nephritis Lupus nephritis is a potentially life-threatening manifestation of systemic lupus erythematosus, an autoimmune disease that commonly affects the kidneys. Lupus nephritis affects approximately 1.7 million people worldwide. Lupus nephritis has a profound impact on the lives and outlook of those affected and even with the latest treatments, the damage caused to the kidneys usually gets worse over time, with up to a third of people progressing to end-stage kidney disease within 10 years, where the only options are dialysis or transplant. Lupus nephritis predominantly affects women, mostly women of color and usually of childbearing age. Currently, there is no cure. Gazyva U.S. Indications Gazyva ® (obinutuzumab) is a prescription medicine used: With the chemotherapy drug, chlorambucil, to treat chronic lymphocytic leukemia (CLL) in adults who have not had previous CLL treatment. With the chemotherapy drug, bendamustine, followed by Gazyva alone for follicular lymphoma (FL) in adults who did not respond to a rituximab-containing regimen, or whose FL returned after such treatment. In combination with chemotherapy, followed by Gazyva alone in those who responded, to treat stage II bulky, III, or IV FL in adults who have not had previous FL treatment. Important Safety Information The most important safety information patients should know about Gazyva Patients must tell their doctor right away about any side effect they experience. Gazyva can cause side effects that can become serious or life-threatening, including: Hepatitis B Virus (HBV): Hepatitis B can cause liver failure and death. If the patient has a history of hepatitis B infection, Gazyva could cause it to return. Patients should not receive Gazyva if they have active hepatitis B liver disease. The patient’s doctor or healthcare team will need to screen them for hepatitis B before, and monitor the patient for hepatitis during and after, their treatment with Gazyva. Sometimes this will require treatment for hepatitis B. Symptoms of hepatitis include: worsening of fatigue and yellow discoloration of skin or eyes. Progressive Multifocal Leukoencephalopathy (PML): PML is a rare and serious brain infection caused by a virus. PML can be fatal. The patient’s weakened immune system could put them at risk. The patient’s doctor will watch for symptoms. Symptoms of PML include: confusion, difficulty talking or walking, dizziness or loss of balance, and vision problems. Who should not receive Gazyva: Patients should NOT receive Gazyva if they have had an allergic reaction (e.g., anaphylaxis or serum sickness) to Gazyva. Patients must tell their healthcare provider if they have had an allergic reaction to obinutuzumab or any other ingredients in Gazyva in the past. Additional possible serious side effects of Gazyva: Patients must tell their doctor right away about any side effect they experience. Gazyva can cause side effects that may become severe or life threatening, including: Infusion Reactions: These side effects may occur during or within 24 hours of any Gazyva infusion. Some infusion reactions can be serious, including, but not limited to, severe allergic reactions (anaphylaxis), acute life-threatening breathing problems, or other life-threatening infusion reactions. If the patient has a reaction, the infusion is either slowed or stopped until their symptoms are resolved. Most patients are able to complete infusions and receive medication again. However, if the infusion reaction is life-threatening, the infusion of Gazyva will be permanently stopped. The patient’s healthcare team will take steps to help lessen any side effects the patient may have to the infusion process. The patient may be given medicines to take before each Gazyva treatment. Symptoms of infusion reactions may include: fast heartbeat, tiredness, dizziness, headache, redness of the face, nausea, chills, fever, vomiting, diarrhea, rash, high blood pressure, low blood pressure, difficulty breathing, and chest discomfort. Hypersensitivity Reactions Including Serum Sickness: Some patients receiving Gazyva may have severe or life-threatening allergic reactions. This reaction may be severe, may happen during or after an infusion, and may affect many areas of the body. If an allergic reaction occurs, the patient’s doctor will stop the infusion and permanently discontinue Gazyva. Tumor Lysis Syndrome (TLS): Tumor lysis syndrome, including fatal cases, has been reported in patients receiving Gazyva. Gazyva works to break down cancer cells quickly. As cancer cells break apart, their contents are released into the blood. These contents may cause damage to organs and the heart, and may lead to kidney failure requiring the need for dialysis treatment. The patient’s doctor may prescribe medication to help prevent TLS. The patient’s doctor will also conduct regular blood tests to check for TLS. Symptoms of TLS may include nausea, vomiting, diarrhea, and tiredness. Infections: While the patient is taking Gazyva, they may develop infections. Some of these infections may be fatal and severe, so the patient should be sure to talk to their doctor if they think they have an infection. Patients administered Gazyva in combination with chemotherapy, followed by Gazyva alone are at a high risk of infections during and after treatment. Patients with a history of recurring or chronic infections may be at an increased risk of infection. Patients with an active infection should not be treated with Gazyva. Patients taking Gazyva plus bendamustine may be at higher risk for fatal or severe infections compared to patients taking Gazyva plus CHOP or CVP. Low White Blood Cell Count: When the patient has an abnormally low count of infection-fighting white blood cells, it is called neutropenia. While the patient is taking Gazyva, their doctor will do blood work to check their white blood cell count. Severe and life-threatening neutropenia can develop during or after treatment with Gazyva. Some cases of neutropenia can last for more than one month. If the patient’s white blood cell count is low, their doctor may prescribe medication to help prevent infections. Low Platelet Count: Platelets help stop bleeding or blood loss. Gazyva may reduce the number of platelets the patient has in their blood; having low platelet count is called thrombocytopenia. This may affect the clotting process. While the patient is taking Gazyva, their doctor will do blood work to check their platelet count. Severe and life-threatening thrombocytopenia can develop during treatment with Gazyva. Fatal bleeding events have occurred in patients treated with Gazyva. If the patient’s platelet count gets too low, their treatment may be delayed or reduced. Disseminated Intravascular Coagulation (DIC): Fatal and severe DIC has been reported in people receiving GAZYVA. DIC is a rare and serious abnormal blood clotting condition that should be monitored and managed by your doctor as it can lead to uncontrollable bleeding The most common side effects of Gazyva in CLL were infusion-related reactions and low white blood cell counts. The most common side effects seen with GAZYVA in a study that included relapsed or refractory NHL, including FL patients were infusion-related reactions, fatigue, low white blood cell counts, cough, upper respiratory tract infection, and joint or muscle pain. The most common side effects seen with GAZYVA in a study that included previously untreated FL patients were infusion-related reactions, low white blood cell count, upper respiratory tract infections, cough, constipation and diarrhea. Before receiving Gazyva, patients should talk to their doctor about: Immunizations: Before receiving Gazyva therapy, the patient should tell their healthcare provider if they have recently received or are scheduled to receive a vaccine. Patients who are treated with Gazyva should not receive live vaccines. Pregnancy: The patient should tell their doctor if they are pregnant, think that they might be pregnant, or plan to become pregnant. Gazyva may harm their unborn baby. The patient should speak to their doctor about using Gazyva while they are pregnant. The patient should talk to their doctor or their child’s doctor about the safety and timing of live virus vaccinations to their infant if they received Gazyva during pregnancy. Patients of childbearing potential should use effective contraception while taking Gazyva and for 6 months after your Gazyva treatment. Breastfeeding: Because of the potential risk of serious side reactions in breastfed children, patient should not breastfeed while taking Gazyva and for 6 months after your last dose. Patients should tell their doctor about any side effects. These are not all of the possible side effects of Gazyva. For more information, patients should ask their doctor or pharmacist. Gazyva is available by prescription only. Report side effects to the FDA at (800) FDA-1088, or http://www.fda.gov/medwatch. Report side effects to Genentech at (888) 835-2555. Please visit https://www.Gazyva.com for the Gazyva full Prescribing Information, including BOXED WARNINGS, for additional Important Safety Information. About Genentech in Kidney Diseases For 20 years, we have combined innovation, scientific expertise and commitment to patients to address unmet needs in kidney diseases. Our industry-leading pipeline includes several ongoing Phase I-III clinical studies of immune-mediated investigational therapies with the aim of bringing innovative new treatment options to people living with kidney and kidney-related diseases, including lupus nephritis, membranous nephropathy, immunoglobulin A nephropathy, atypical hemolytic uremic syndrome, childhood-onset idiopathic nephrotic syndrome and systemic lupus erythematosus, an autoimmune disease that can lead to lupus nephritis. About Genentech Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com .