ADO-Trastuzumab Emtansine

Recommendation based on DESTINY-Breast05 phase 3 trial results that showed Enhertu reduced the risk of invasive disease recurrence or death by 53% versus T-DM1 Daiichi Sankyo and AstraZeneca’s Enhertu has the potential to become a new standard of care in this early breast cancer setting TOKYO--(BUSINESS WIRE)--Enhertu ® (trastuzumab deruxtecan) has been recommended for approval in the European Union (EU) as a monotherapy for the adjuvant treatment of adult patients with resected HER2 positive breast cancer who have residual invasive disease after neoadjuvant taxane-based and HER2 targeted treatment. Enhertu is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/NYSE: AZN). The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on results from the DESTINY-Breast05 phase 3 trial presented at the 2025 European Society for Medical Oncology (#ESMO25) Congress and subsequently published in The New England Journal of Medicine . The recommendation will now be reviewed by the European Commission, which has the authority to grant marketing authorizations for medicines in the EU. In DESTINY-Breast05, Enhertu significantly reduced the risk of invasive disease recurrence or death (invasive disease-free survival [IDFS]) by 53% (hazard ratio [HR]=0.47; 95% confidence interval [CI]: 0.34-0.66; p<0.0001) compared to trastuzumab emtansine (T-DM1) in patients with HER2 positive breast cancer with residual invasive disease following neoadjuvant therapy. Enhertu demonstrated a three-year IDFS rate of 92.4% (95% CI: 89.7-94.4) and 83.7% with T-DM1 (95% CI: 80.2-86.7). Data also showed that Enhertu significantly reduced the risk of disease recurrence or death (disease-free survival [DFS]) by 53% (HR=0.47; 95% CI: 0.34-0.66; p<0.0001) compared to T-DM1. Results showed a three-year DFS rate of 92.3% (95% CI: 89.5-94.3) in the Enhertu arm and 83.5% with T-DM1 (95% CI: 79.9-86.4). “Patients with HER2 positive early breast cancer who have residual disease after neoadjuvant treatment experience a substantially higher risk of recurrence, making effective adjuvant treatment especially important,” said John Tsai, MD, Global Head, R&D, Daiichi Sankyo. “This positive CHMP opinion underscores the potential role of Enhertu in the curative-intent setting where it is critical to maximize the potential for sustained long-term outcomes.” “This positive CHMP opinion marks a significant step towards bringing Enhertu into early-stage HER2 positive breast cancer in the EU,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology Hematology R&D, AstraZeneca. “Enhertu cut the risk of disease recurrence by more than half compared to adjuvant standard of care for patients with residual disease, and if approved could redefine post-surgery care in the EU, keeping patients disease-free for longer and increasing the potential for cure.” The safety pro Enhertu in DESTINY-Breast05 was consistent with the known pro no new safety concerns identified. The most common treatment-related adverse events that occurred in patients treated with Enhertu were nausea (71.3%), constipation (32.0%), decreased neutrophil count (31.6%) and vomiting (31.0%). Interstitial lung disease (ILD) or pneumonitis occurred in 9.6% of patients treated with Enhertu as determined by an independent adjudication committee. The majority of ILD or pneumonitis events were low grade (grade 1 [n=16; 2.0%] or grade 2 [n=52; 6.5%]). There were two grade 5 events (0.2%) of ILD or pneumonitis in the Enhertu arm. Enhertu is approved in Brazil, Canada, India and the U.S. for the adjuvant treatment of adult patients with HER2 positive breast cancer and residual invasive disease following neoadjuvant treatment based on DESTINY-Breast05. About DESTINY-Breast05 DESTINY-Breast05 is a global, multicenter, randomized, open-label, phase 3 trial evaluating the efficacy and safety of Enhertu (5.4 mg/kg) versus T-DM1 in patients with HER2 positive early breast cancer with residual invasive disease in breast or axillary lymph nodes following neoadjuvant therapy and a high risk of recurrence. High risk of recurrence was defined as presentation with inoperable cancer (prior to neoadjuvant therapy) or pathologically positive axillary lymph nodes following neoadjuvant therapy. The primary endpoint of DESTINY-Breast05 is investigator-assessed IDFS, which is defined as the time from randomization until first invasive local, axillary or distant recurrence or death from any cause. The key secondary endpoint is investigator-assessed DFS. Other secondary endpoints include overall survival, distant recurrence-free interval, brain metastases-free interval and safety. DESTINY-Breast05 enrolled 1,635 patients in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov . About HER2 Positive Early Breast Cancer Breast cancer is the most common cancer in women worldwide and the leading cause of cancer-related deaths among women. 1 Approximately 2.4 million breast cancer cases were diagnosed in 2024, with more than 690,000 deaths globally. 1 In Europe, approximately 540,000 cases of breast cancer were diagnosed in 2024, with more than 140,000 deaths. 2 HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast cancer. 3 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer. 3 Approximately one in five cases of breast cancer is considered HER2 positive. 4 Approximately one in three patients with HER2 positive early-stage breast cancer is considered high-risk, meaning they are more likely to experience disease recurrence and have a poor prognosis. 5 The current standard of care in the HER2 positive adjuvant (after surgery) setting for patients with residual invasive disease in the EU is T-DM1. 6 Despite receiving additional treatment with current standard of care for residual disease, some patients still experience invasive disease or death. 7 Once patients are diagnosed with metastatic disease, the five-year survival rate drops from nearly 100% to approximately 34%. 8 Adjuvant therapy represents a key opportunity to minimize the risk of recurrence and prevent progression to metastatic disease for patients with residual disease. 9,10,11 New treatment options are needed in the early breast cancer setting to improve long-term outcomes for more patients. About Enhertu Enhertu (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using the proprietary DXd ADC Technology of Daiichi Sankyo, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. Enhertu (5.4 mg/kg) followed by THP is approved in Brazil, China, India, Singapore, Taiwan and the U.S. as a neoadjuvant treatment for adult patients with HER2 positive (IHC 3+ or ISH+) stage 2 or stage 3 breast cancer based on the results from the DESTINY-Breast11 trial. Continued approval in China for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Enhertu (5.4 mg/kg) is approved in Brazil, Canada, India and the U.S. for the adjuvant treatment of adult patients with HER2 positive breast cancer who have residual invasive disease following neoadjuvant trastuzumab (with or without pertuzumab) and taxane-based treatment based on the DESTINY-Breast05 trial. Enhertu (5.4 mg/kg) in combination with pertuzumab is approved in more than 40 countries/regions worldwide as a first-line treatment for adult patients with unresectable or metastatic HER2 positive (IHC 3+ or ISH+) breast cancer, as determined by a locally or regionally approved test, based on the results from the DESTINY-Breast09 trial. Enhertu (5.4 mg/kg) is approved in more than 100 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+ or ISH+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial. Enhertu (5.4 mg/kg) is approved in more than 75 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic hormone receptor positive, HER2 low (IHC 1+ or IHC 2+/ ISH-) or HER2 ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that have progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial. Enhertu (5.4 mg/kg) is approved in more than 100 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial. Enhertu (5.4 mg/kg) is approved in more than 80 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 ( ERBB2 ) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the U.S. for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Enhertu (6.4 mg/kg) is approved in more than 90 countries/regions worldwide for the treatment of adult patients with locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 , DESTINY-Gastric02 and/or DESTINY-Gastric04 trials. Enhertu (5.4 mg/kg) is approved in more than 45 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02 , DESTINY-Lung01 , DESTINY-CRC02 and/or HERALD trials. Continued approval in the U.S. for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. About the Enhertu Clinical Development Program A comprehensive global clinical development program is underway evaluating the efficacy and safety of Enhertu as a monotherapy or in combination or sequentially with other cancer medicines across multiple HER2 targetable cancers. About the Daiichi Sankyo and AstraZeneca Collaboration Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize Enhertu in March 2019 and Datroway ® in July 2020 , except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and Datroway. About the ADC Portfolio of Daiichi Sankyo The Daiichi Sankyo ADC portfolio consists of nine ADCs in clinical development crafted from ADC technology discovered in-house by Daiichi Sankyo. The DXd ADC Technology platform of Daiichi Sankyo consists of seven ADCs in clinical development where each ADC is comprised of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADCs include Enhertu and Datroway, which are being jointly developed and commercialized globally with AstraZeneca, and ifinatamab deruxtecan (I-DXd), raludotatug deruxtecan (R-DXd) and patritumab deruxtecan (HER3-DXd), which are being jointly developed and commercialized globally with Merck & Co., Inc, Rahway, NJ, USA. DS-3939 and DS3790 are being developed by Daiichi Sankyo. Additional ADCs being developed by Daiichi Sankyo include DS3610, which consists of an antibody attached to a novel payload that acts as an agonist of STING, and DS1025, which consists of a CD25 directed antibody attached to an immuno-oncology optimized cytotoxic payload. Ifinatamab deruxtecan, raludotatug deruxtecan, patritumab deruxtecan, DS-3939, DS3610, DS3790 and DS1025 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established. About Daiichi Sankyo Daiichi Sankyo (TSE: 4568) is a global healthcare company committed to becoming a trusted healthcare innovator, transforming the lives of people through its strength in science and technology. The company discovers and develops new standards of care to address diverse medical needs to fulfill its purpose of contributing to the enrichment of quality of life around the world. With a strategic focus on oncology, Daiichi Sankyo is advancing an industry-leading antibody drug conjugate portfolio along with identifying new breakthrough generating technologies to deliver practice-changing medicines to patients, healthcare professionals and society. For more information, please visit . REFERENCES: 1 World Health Organization. Global Status Report On Cancer 2026: The Future We Choose Together . Accessed September 2026. 2 World Health Organization. Breast Fact Sheet . Accessed September 2026. 3 Cheng X. Genes . 2024;15(7):903. 4 Tarantino P, et al. Ann Oncol . 2023;34(8):645-659. 5 Mahtani R, et al. Cancers (Basel). 2025;17(11):1848. 6 Loibl S, et al. ESMO Clinical Practice Guidelines . 2024. 7 Geyer CE, et al. N Engl J Med . 2025;392(3):249-257. 8 National Cancer Institute. SEER Cancer Stat Facts: Female Breast Cancer Subtypes . Accessed September 2026. 9 von Minckwitz G, et al. N Engl J Med . 2019;380(7):617-628. 10 Zaborowski AM and Wong SM. BJS . 2023;110(7):765-772. 11 Loibl S, et al. N Engl J Med . 2026;394(9):845-857 . Contacts MEDIA CONTACTS: Global: Jennifer Brennan jennifer.brennan@daiichisankyo.com +1 908 900 3183 (mobile) EU: Simone Jendsch-Dowé simone.jendsch-dowe@daiichisankyo.com +49 (89) 78080 (office) Japan: DS-PR_jp@daiichisankyo.com INVESTOR RELATIONS CONTACT: DaiichiSankyoIR_jp@daiichisankyo.com

New data presented in Vienna highlights long-term repeat-dose modeling, mechanistic GI barrier profiling, and deconvolution of payload- and linker-dependent toxicities for complex modalities SAN DIEGO, Sept. 16, 2026 (GLOBE NEWSWIRE) -- VivoSim Labs, Inc. (NASDAQ: VIVS) (“VivoSim” or the “Company”) unveils new clinical benchmark data at the 58th Congress of the European Societies of Toxicology (EUROTOX 2026) in Vienna, Austria, demonstrating the ability of its NAMkind™ 3D human liver and intestinal platforms to predict drug toxicity across small molecules and increasingly complex therapies, including Antibody-Drug Conjugates (ADCs). The new data strengthens VivoSim's positioning in the growing market for human-relevant predictive toxicology and New Approach Methodologies (NAMs), as pharmaceutical companies increasingly look for better ways to identify safety risks before drug candidates enter expensive human clinical trials. Drug-induced liver injury (DILI) and gastrointestinal (GI) toxicity remain leading causes of drug candidate attrition, while ADC therapies introduce additional safety challenges involving payload toxicity, linker behavior and off-target exposure. VivoSim's EUROTOX findings demonstrate how its long-duration, primary human cell-based models can help identify and differentiate these risks earlier in development, successfully ranking clinical safety risks for small-molecule reference sets such as thiazolidinediones and NSAIDs, while deconvoluting complex structural toxicities in advanced ADC modalities. NAMkind™ Targets Liver and GI Toxicity Before the Clinic VivoSim's NAMkind™ Liver platform supports up to 28-day liver spheroid viability, while its intestinal models maintain barrier integrity for up to three weeks, allowing researchers to evaluate repeat-dose effects that shorter-duration laboratory assays may not capture. In studies being presented at EUROTOX, VivoSim's repeat-dose testing framework successfully ranked clinical safety risks across small-molecule reference compounds while also distinguishing payload- and linker-dependent toxicities in ADCs. The NAMkind™ Liver platform ranked trastuzumab deruxtecan as significantly more hepatotoxic than trastuzumab emtansine in the presented testing. In the NAMkind™ Intestine model, transepithelial electrical resistance (TEER) identified mucosal barrier deterioration before overt tissue cytotoxicity, with human ileum tissue demonstrating greater sensitivity to ADC-induced toxicity than colon tissue. The findings carry particular weight as ADC development expands across oncology and other therapeutic areas, sharpening demand for technologies capable of determining where toxicity originates and which component of a complex drug is responsible. Moving Beyond Detecting Toxicity The broader commercial opportunity for VivoSim goes beyond simply detecting whether a drug candidate is toxic: it lies in helping pharmaceutical developers understand why toxicity occurs and whether it is likely to matter in humans. “As global regulators like the FDA accelerate the transition away from traditional animal testing, biopharma leaders are seeking predictive human tools that eliminate translational surprises before clinical entry,” said Keith Murphy, Executive Chairman of VivoSim Labs. “Our latest data presented at EUROTOX demonstrate that the NAMkind™ platform doesn't just evaluate traditional small molecules with exceptional fidelity, it successfully deconvolutes the complex safety liabilities of next-generation modalities like ADCs. By identifying payload and linker toxicities early, we provide our commercial partners with the actionable intelligence needed to save years of development and millions in potential clinical failure.” “Predicting organ-specific toxicity requires capturing the biology of chronic, repeat-dose exposure,” said Amar Sethi, M.D., Ph.D., Chief Scientific Officer of VivoSim Labs. “With our extended-culture platforms, we observe micro-architectural and functional degradation that traditional short-term assays may miss. Whether ranking clinical DILI risk across small-molecule analogs or pinpointing why trastuzumab deruxtecan exhibits distinct hepatic and ileal liabilities compared to emtansine, our multi-endpoint profiling gives biopharma teams human-relevant translational signatures to optimize compound selection and de-risk pipelines.” FDA NAM Momentum Adds to the Opportunity The EUROTOX presentation arrives as regulators, including the U.S. Food and Drug Administration (FDA), continue advancing frameworks for New Approach Methodologies and human-relevant alternatives to traditional animal testing. That regulatory shift does not represent an endorsement of VivoSim specifically, but it creates a potentially favorable industry backdrop for validated technologies capable of generating predictive human safety information before clinical development. The opportunity extends beyond detecting toxicity. If broader validation and pharmaceutical adoption follow, NAMkind™ and VitroSense™ could become part of the decision layer between drug discovery and human clinical trials, helping pharmaceutical companies determine which programs deserve additional time and development capital. For VivoSim investors, the EUROTOX data mark a meaningful validation point in the developing commercial thesis behind NAMkind™ using 3D human biology and predictive toxicology to help pharmaceutical companies identify safety liabilities earlier, select stronger drug candidates and reduce costly failures later in development. VivoSim's demonstrated ability to evaluate both traditional small molecules and increasingly important complex modalities such as ADCs positions its NAMkind™ platform to broaden its applications across pharmaceutical R&D. About VivoSim Labs VivoSim Labs, Inc. (“VivoSim” and the “Company”), is a pharmaceutical and biotechnology services company that is focused on providing testing of drugs and drug candidates in three-dimensional (“3D”) human tissue models of liver and intestine. The Company offers partners liver and intestinal toxicology insights using its new approach methodologies (“NAM”) models. The Company anticipates accelerated adoption of human tissue models following the U.S. Food and Drug Administration (“FDA”) Roadmap to refine animal testing requirements in favor of these non-animal NAM methods. VivoSim Labs operates from San Diego, CA. Visit . Forward-Looking Statements Any statements contained in this press release that do not describe historical facts constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995. Any forward-looking statements contained herein are based on current expectations but are subject to a number of risks and uncertainties. Forward-looking statements include statements regarding the Company’s cash on hand, revenue growth guidance and the Company’s progress in marketing contract research services using NAMs models to pharmaceutical companies. Such forward-looking statements are not guarantees of performance and actual actions or events could differ materially from those contained in such statements. These risks and uncertainties and other factors are identified and described in more detail in the Company’s filings with the SEC, including its Annual Report on Form 10-K filed with the SEC on July 14, 2026, as such risk factors are updated in its most recently filed Quarterly Report on Form 10-Q filed with the SEC on August 12, 2026. You should not place undue reliance on these forward-looking statements, which speak only as of the date that they were made. These cautionary statements should be considered with any written or oral forward-looking statements that the Company may issue in the future. Except as required by applicable law, including the securities laws of the United States, the Company does not intend to update any of the forward-looking statements to conform these statements to reflect actual results, later events, or circumstances or to reflect the occurrence of unanticipated events. Contact: Investor Relations info@vivosim.ai VivoSim Labs, Inc.