Pemetrexed Dipotassium

– 17 abstracts and presentations planned at SSIEM Symposium – – Real-world evidence demonstrates significant diet liberalization achieved with Sephience while maintaining target blood Phe levels – – Continued evidence of meaningful benefit across all patient subgroups – WARREN, N.J., Aug. 24, 2026 /PRNewswire/ -- PTC Therapeutics, Inc. (NASDAQ: PTCT) today announced that multiple Sephience™ (sepiapterin) scientific data presentations will be featured at the 2026 Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Symposium, taking place in Helsinki, Finland, from Aug. 25-28. The presentations include new data from clinical trials and real-world evidence which reinforce the clinically meaningful benefits of Sephience on lowering phenylalanine (Phe), significant diet liberalization and sustained metabolic control for the full spectrum of individuals living with phenylketonuria (PKU) including those with classical PKU. In addition, Sephience studies continue to show a consistent and favorable safety profile. "The SSIEM presentations further demonstrate the broad clinical benefits of Sephience across the full spectrum of individuals living with PKU," said Matthew B. Klein, M.D., Chief Executive Officer. "In addition, new data to be presented at the PTC symposium show treatment with Sephience led to a large number of responsive participants achieving normalization of blood Phe levels (<120 µmol/L) in a rapid timeframe, including those with classical or non-BH4-responsive PKU. These impressive data support the potential benefits Sephience can deliver for individuals affected by PKU." Highlights of the data to be presented at SSIEM 2026 include: New analyses from the AMPLIPHY study demonstrate that Sephience treatment resulted in a 100% greater reduction in blood Phe for participants on sapropterin at screening after switching to Sephience. In an analysis of participants in Sephience studies with high baseline Phe levels (≥900 µmol/L), Sephience treatment resulted in clinically meaningful reductions in blood Phe levels within 14 days, with response rates comparable to the overall study population, and a safety profile consistent with prior studies. These findings support a trial of Sephience treatment in individuals with PKU regardless of severity or baseline Phe. An analysis of real-world data performed by a leading global key opinion leader shows that Sephience enabled significant dietary liberalization in adolescents, supporting greater independence, reduced dietary burden, and maintained metabolic control within recommended targets. These results were observed in individuals with both BH4-responsive and classical/non-BH4 responsive PKU mutations. About Sephience™ (sepiapterin) Sephience™ is indicated for the treatment of adult and pediatric patients with phenylketonuria (PKU). Sephience is a natural precursor of the enzymatic co-factor BH4, a critical co-factor for phenylalanine hydroxylase (PAH). Through its unique dual mechanism of action, Sephience is able to effectively reduce blood phenylalanine (Phe) levels and has the potential to treat a broad range of PKU patients. Sephience is approved in the United States, the European Union/European Economic Area region, Japan and other countries. Indication and Important Safety Information Indication SEPHIENCE is indicated for the treatment of hyperphenylalaninemia (HPA) in adult and pediatric patients 1 month of age and older with sepiapterin-responsive phenylketonuria (PKU). SEPHIENCE is to be used in conjunction with a phenylalanine (Phe)-restricted diet. Contraindications None. Important Safety Information Treatment with SEPHIENCE should be directed by physicians knowledgeable in the management of PKU. Biochemical response to SEPHIENCE can only be determined by a therapeutic trial with careful monitoring of ongoing dietary and nutritional balance to ensure adequate Phe control. Warnings and Precautions Increased Bleeding: SEPHIENCE may increase the risk of bleeding. Bleeding events, including superficial hematomas, prolonged bleeding, and heavy menstrual bleeding have occurred in patients treated with SEPHIENCE. Inform patients about the risk of bleeding associated with SEPHIENCE and have patients follow up with their healthcare provider should such a bleeding event occur. Consider treatment interruption with SEPHIENCE in patients with active bleeding. Hypophenylalaninemia: Some pediatric patients receiving SEPHIENCE experienced hypophenylalaninemia. Monitor blood Phe levels during treatment and modify the dosage of SEPHIENCE and/or dietary protein and Phe intake as needed to ensure adequate blood Phe level control. Frequent blood monitoring is recommended in the pediatric population. Interaction with Levodopa: In a 10-year post-marketing safety surveillance program for a non-PKU indication using another drug that is a phenylalanine hydroxylase (PAH) activator, three patients with underlying neurological disorders experienced seizures, exacerbation of seizures, over-stimulation, and irritability during co-administration with levodopa. Monitor patients who are receiving levodopa for changes in neurological status during treatment with SEPHIENCE. Adverse Reactions Most common adverse reactions with SEPHIENCE (≥2% and > placebo) were diarrhea, headache, abdominal pain, hypophenylalaninemia, feces discoloration and oropharyngeal pain. Drug Interactions Avoid concomitant use of drugs known to inhibit folate synthesis dihydrofolate reductase (DHFR) (e.g., trimethoprim, methotrexate, trimetrexate, pemetrexed, pralatrexate, raltitrexed, and piritrexim) while taking SEPHIENCE. Concomitant administration of such drugs may reduce sepiapterin metabolism to BH4. If concomitant use is not avoidable, monitor blood Phe levels. SEPHIENCE and PDE-5 inhibitors (e.g., sildenafil, vardenafil, or tadalafil) induce vasorelaxation and may reduce blood pressure. Monitor for signs and symptoms of hypotension. For medical information, product complaints, or to report an adverse event, please call 1-866-562-4620 or email [email protected]. You may also report adverse events directly to FDA at 1-800-FDA-1088 or . Please see Full Prescribing Information. About Phenylketonuria Phenylketonuria (PKU) is a rare, inherited metabolic disease, characterized by the body's inability to break down an essential amino acid called phenylalanine (Phe) and which can result in neurological and other symptoms. If left untreated or poorly managed, Phe can build up to harmful levels in the body. This causes severe and irreversible disabilities, such as permanent intellectual disability, seizures, delayed development, memory loss, and behavioral and emotional problems. Newborns with PKU initially do not have any symptoms, but symptoms are usually progressive, and damage caused by toxic levels of Phe in the first few years of life is irreversible. Diagnosis of PKU usually takes place during newborn screening programs. There are an estimated 58,000 people living with PKU globally. About PTC Therapeutics, Inc. PTC is a global biopharmaceutical company dedicated to the discovery, development and commercialization of clinically differentiated medicines for children and adults living with rare disorders. PTC is advancing a robust and diversified pipeline of transformative medicines as part of its mission to provide access to best-in-class treatments for patients with unmet medical needs. The company's strategy is to leverage its scientific expertise and global commercial infrastructure to optimize value for patients and other stakeholders. To learn more about PTC, please visit and follow us on LinkedIn, X, Instagram and Facebook. For More Information: Investors: Ellen Cavaleri +1 (615) 618-6228 [email protected] Media: Jeanine Clemente +1 (908) 912-9406 [email protected] Forward-Looking Statements: This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. All statements contained in this release, other than statements of historic fact, are forward-looking statements, including statements regarding: the future expectations, plans and prospects for PTC, including with respect to the expected timing of clinical trials and studies, availability of data, regulatory submissions and responses, commercialization and other matters with respect to its products and product candidates; expectations with respect to Sephience; PTC's strategy, future operations, future financial position, future revenues, projected costs; and the objectives of management. Other forward-looking statements may be identified by the words, "guidance", "plan," "anticipate," "believe," "estimate," "expect," "intend," "may," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions. PTC's actual results, performance or achievements could differ materially from those expressed or implied by forward-looking statements it makes as a result of a variety of risks and uncertainties, including those related to: the outcome of pricing, coverage and reimbursement negotiations with third party payors for PTC's products or product candidates that PTC commercializes or may commercialize in the future; expectations with respect to Sephience, including commercialization and the potential achievement of sales milestones and contingent payments that PTC may be obligated to make; significant business effects, including the effects of industry, market, economic, political or regulatory conditions; changes in tax and other laws, regulations, rates and policies; the eligible patient base and commercial potential of PTC's products and product candidates; PTC's scientific approach and general development progress; and the factors discussed in the "Risk Factors" section of PTC's most recent Annual Report on Form 10-K, as well as any updates to these risk factors filed from time to time in PTC's other filings with the SEC. You are urged to carefully consider all such factors. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval, and commercialization of new products. There are no guarantees that any product will receive or maintain regulatory approval in any territory, or prove to be commercially successful, including Sephience. The forward-looking statements contained herein represent PTC's views only as of the date of this press release and PTC does not undertake or plan to update or revise any such forward-looking statements to reflect actual results or changes in plans, prospects, assumptions, estimates or projections, or other circumstances occurring after the date of this press release except as required by law. SOURCE PTC Therapeutics, Inc. 21% more press release views with Request a Demo

Daiichi Sankyo and AstraZeneca’s Enhertu is the first and only HER2 directed medicine to improve progression-free survival over global standard of care in a phase 3 trial in this setting Data to be presented at an upcoming medical meeting and shared with global regulatory authorities TOKYO--(BUSINESS WIRE)--Positive topline results from the DESTINY-Lung04 phase 3 trial showed Enhertu ® (trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus global standard of care (platinum-pemetrexed doublet chemotherapy plus pembrolizumab) as first-line treatment of patients with unresectable, locally advanced or metastatic HER2 mutant non-squamous non-small cell lung cancer (NSCLC). The trial will continue as planned to evaluate secondary endpoints including overall survival. 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). Global standard of care for patients with HER2 mutant NSCLC in the first-line metastatic setting is a combination of immunotherapy and platinum-based chemotherapy. 1,2,3 However, many patients do not respond to first-line treatment and experience disease progression, underscoring the need for additional treatment options. 3,4,5,6,7 Approximately 2% to 4% of patients with NSCLC have tumors with a HER2 mutation. 8,9,10,11 “Enhertu is already established as the first and only antibody drug conjugate for the second-line treatment of HER2 mutant metastatic non-small cell lung cancer,” said John Tsai, MD, Global Head of R&D, Daiichi Sankyo. “The positive results seen in DESTINY-Lung04 show that treatment with Enhertu in the first-line setting delays disease progression compared to the global standard of care, highlighting its potential to improve outcomes for patients earlier in the treatment of metastatic disease.” “Our oncology pipeline continues to advance with DESTINY-Lung04 becoming the first phase 3 trial to demonstrate a progression-free survival benefit versus the global standard of care in this first-line setting, supporting the potential for Enhertu to move earlier in the treatment of HER2 mutant non-small cell lung cancer,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology Hematology R&D, AstraZeneca. “This aggressive lung cancer often affects younger patients and has historically had limited first-line targeted treatment options, making these positive results an important step forward in bringing additional effective therapies to patients at metastatic diagnosis when there is the greatest opportunity to improve outcomes.” The safety pro Enhertu observed in DESTINY-Lung04 was generally consistent with its known pro no new safety concerns identified. The DESTINY-Lung04 data will be presented at an upcoming medical meeting and shared with global regulatory authorities. Enhertu is currently approved in more than 80 countries/regions to treat patients with previously treated metastatic NSCLC whose tumors have activating HER2 ( ERBB2 ) mutations and in more than 45 countries/regions to treat patients with HER2 positive solid tumors, including HER2 overexpressing metastatic NSCLC, who have received prior treatment and who have no satisfactory treatment options. About DESTINY-Lung04 DESTINY-Lung04 is a global, randomized, open-label, phase 3 trial evaluating the efficacy and safety of Enhertu (5.4 mg/kg) compared to standard of care (platinum-pemetrexed doublet chemotherapy in combination with pembrolizumab) in patients with unresectable, locally advanced or metastatic, non-squamous NSCLC harboring a HER2 exon 19 or 20 mutation. Patients were randomized 1:1 to receive either Enhertu or standard of care. Randomization was stratified by smoking history and presence or history of brain metastasis. The primary endpoint of DESTINY-Lung04 is PFS as assessed by blinded independent central review (BICR). Secondary endpoints include OS, investigator-assessed PFS, overall response rate and duration of response as assessed by BICR and investigator, pharmacokinetics and safety. DESTINY-Lung04 enrolled 454 patients across multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov . About HER2 Mutant NSCLC Lung cancer is the most commonly diagnosed cancer globally and remains the leading cause of cancer-related death. 12 In 2024, approximately 2.6 million new lung cancer cases were reported worldwide, with an estimated 1.8 million deaths. 12 NSCLC is the most common type of lung cancer, accounting for approximately 85% of cases. 13 Prognosis is particularly poor for patients with metastatic NSCLC as only approximately 10% will live beyond five years after diagnosis. 14,15,16 HER2 is a tyrosine kinase receptor protein involved in cell growth and differentiation and expressed on the surface of multiple tumor types. HER2 mutations have been identified in NSCLC as distinct molecular targets and have been reported in approximately 2% to 4% of patients with non-squamous NSCLC. 8,9,10,11 These HER2 mutations are predominantly seen in younger women and people with no smoking history and have been independently associated with cancer cell growth and poor prognosis, with an increased incidence of brain metastases. 8,17,18,19,20,21 Traditionally the global standard of care in the first-line metastatic setting of patients with HER2 mutant NSCLC has been a combination of immunotherapy and platinum-based chemotherapy. 1,2,3 While these treatment regimens have been shown to improve survival in NSCLC, many patients do not respond to first-line treatment and experience disease progression, underscoring the need for additional treatment options. 3,4,5,6,7 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 China, India, Singapore 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 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 Brazil, China, India, Israel, Saudi Arabia, Singapore, South Korea, Switzerland, Taiwan, the United Arab Emirates and the U.S. 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 (HR) 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. Enhertu U.S. Indications and Important Safety Information Indications ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for: HER2-Positive Early Breast Cancer As neoadjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) Stage II or III breast cancer, as determined by an FDA-authorized test followed by a taxane, trastuzumab, and pertuzumab (THP) As monotherapy in adult patients with HER2-positive (IHC 3+ or ISH+) breast cancer who have residual invasive disease after neoadjuvant HER2-targeted treatment HER2-Positive Metastatic Breast Cancer In combination with pertuzumab as first-line treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer, as determined by an FDA-authorized test As monotherapy 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 HER2-Low and HER2-Ultralow Metastatic Breast Cancer As monotherapy for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by an FDA-authorized test, that has progressed on one or more endocrine therapies in the metastatic setting As monotherapy for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-authorized test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy HER2-Mutant Unresectable or Metastatic Non-Small Cell Lung Cancer (NSCLC) As monotherapy for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-authorized test, and who have received a prior systemic therapy This indication is approved under accelerated approval based on objective 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. HER2-Positive Locally Advanced or Metastatic Gastric Cancer As monotherapy for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH positive) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors As monotherapy 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 This indication is approved under accelerated approval based on objective 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. Important Safety Information WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY Interstitial lung disease (ILD) and pneumonitis, including severe, life-threatening, and fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to immediately report symptoms. Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception. Contraindications None. Warnings and Precautions Interstitial Lung Disease / Pneumonitis Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose 1 level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks. HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg) ENHERTU as Monotherapy In patients treated with ENHERTU 5.4 mg/kg, ILD occurred in 12% of patients. Median time to first onset was 5.5 months (range: 0.9 to 31.5). Fatal outcomes due to ILD and/or pneumonitis occurred in 0.9% of patients treated with ENHERTU. ENHERTU in Combination with Pertuzumab In patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), ILD occurred in 12% of patients. Median time to first onset was 8.0 months (range: 0.6 to 33.8). Fatal outcomes due to ILD and/or pneumonitis occurred in 0.5% of patients treated with ENHERTU in combination with pertuzumab. ENHERTU followed by THP In patients treated with ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11, ILD occurred in 4.4% of patients. Median time to first onset was 2.7 months (range: 1.1 to 6.0). Fatal outcomes due to ILD and/or pneumonitis occurred in 1 patient (0.3%) treated with ENHERTU followed by THP. HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg) In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range: 1.2 to 21). Neutropenia Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] 38.3º C or a sustained temperature of ≥38º C for more than 1 hour), interrupt ENHERTU until resolved, then reduce dose by 1 level. HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg) ENHERTU as Monotherapy In patients treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 65% of patients. Nineteen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 22 days (range: 2 to 939). Febrile neutropenia was reported in 1% of patients. ENHERTU in Combination with Pertuzumab In patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), decreased neutrophil count occurred in 79% of patients. Median time to first onset was 22 days (range: 5 to 994). Twenty-nine percent had Grade 3 or 4 decreased neutrophil count. Febrile neutropenia was reported in 2.6% of patients. ENHERTU followed by THP In patients treated with ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11, a decrease in neutrophil count was reported in 58% of patients. Seventeen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 42 days (range: 11 to 165). Febrile neutropenia was reported in 0.9% of patients. HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg) In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 16 days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of patients. Left Ventricular Dysfunction Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular dysfunction (LVD) has been observed with anti-HER2 therapies, including ENHERTU. Assess left ventricular ejection fraction (LVEF) prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVD through treatment interruption. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is 20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of 20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment. HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg) ENHERTU as Monotherapy In patients treated with ENHERTU 5.4 mg/kg, LVD was reported in 4.6% of patients, of which 0.6% were Grade 3 or 4. ENHERTU in Combination with Pertuzumab In patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), LVEF decrease was reported in 11% of patients, of which 2.1% were Grade 3 or 4. ENHERTU followed by THP In patients treated with ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11, LVD was reported in 1.3% of patients, of which 0.3% were Grade 3. HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg) In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography, 8% were found to have asymptomatic Grade 2 decrease in LVEF. Embryo-Fetal Toxicity ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for 7 months after the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose of ENHERTU. Additional Dose Modifications Thrombocytopenia For Grade 3 thrombocytopenia (platelets <50 to 25 x 10 9 /L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 10 9 /L) interrupt ENHERTU until resolved to Grade 1 or less, then reduce dose by 1 level. Radiotherapy-Related Pneumonitis and Skin Injury in the Post-Neoadjuvant Early Breast Cancer Setting Among patients receiving sequential or concurrent adjuvant radiotherapy in DESTINY-Breast05, radiation pneumonitis occurred in 31% of patients receiving ENHERTU 5.4 mg/kg (N=757) and 31% of patients receiving ado-trastuzumab emtansine (T-DM1) 3. Contacts MEDIA CONTACTS: Global: Jennifer Brennan jennifer.brennan@daiichisankyo.com +1 908 900 3183 (mobile) Japan: DS-PR_jp@daiichisankyo.com INVESTOR RELATIONS CONTACT: DaiichiSankyoIR_jp@daiichisankyo.com Read full story here