Steroid hormone receptor

TUESDAY, June 6, 2023 -- Here's some good news for women with the most common type of breast cancer: Adding a targeted breast cancer drug to hormonal therapy reduced the risk of cancer returning by 25% for women with early-stage disease, a new clinical trial shows. Hormone-receptor (HR) positive/HER2 negative breast cancer accounts for about 70% of breast cancer cases in the United States. “The results from the clinical trial have immediate implications for patients,” said Dr. Dennis Slamon , director of clinical and translational research at the University of California, Los Angeles (UCLA) Comprehensive Cancer Center. “The findings show this combination is a treatment of choice for patients with stage 2 or stage 3 HR positive/HER2 negative breast cancer,” he added in a university news release. Patients with HR positive/HER2 negative breast cancer who took the combination therapy -- the drug ribociclib (Kisqali) and standard hormone therapy -- had substantially longer invasive disease-free survival compared to those who were treated with hormone therapy alone. That was true whether or not the cancer had spread to the lymph nodes, the researchers said. Slamon shared the results on Friday at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago. Such research is considered preliminary until published in a peer-reviewed journal. Ribociclib is already FDA-approved to treat metastatic breast cancer, meaning cancer that's advanced. It is one of three cyclin-dependent kinase inhibitors (CDK4/6 inhibitors) approved for combination treatment with standard hormone therapies. However, it is priced up to $15,000 a month, according to drug maker Novartis, which funded the new trial. And CNN reported that a recent analysis suggested it is not a cost-effective treatment, even in its use in people with advanced cancer. In the new clinical trial, more than 5,100 patients with stage 2 or stage 3 early HR positive/HER2 negative breast cancer were randomized into two groups. More than 2,500 were given the combination treatment and more than 2,500 others received only the hormone therapy. Researchers followed with study participants for roughly 34 months. About 20% of the participants were treated with ribociclib for three years and 57% for two years. The invasive disease-free survival rates at three years were about 90%, compared to just over 87% for women who were treated with only hormone therapy. “Overall, the combination therapy showed more favorable outcomes, significantly reducing the risk of the cancer returning,” Slamon said. “These results should change how we evaluate and treat patients.” Sources University of California, Los Angeles, news release, June 2, 2023 Posted June 2023

5 June 2023 -- Updated results from the TROPION-Lung02 Phase Ib trial showed that, with additional enrolment and follow-up from the initial presentation, datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab with or without platinum-based chemotherapy demonstrated promising clinical activity and no new safety signals in both previously untreated or pretreated patients with advanced or metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations (AGAs). Results will be presented on 6 June in an oral presentation at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (#9004). Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo. More than one million people are diagnosed with advanced stage NSCLC each year. 1,2 While 1st-line treatment with immune checkpoint inhibitors with or without chemotherapy has improved outcomes for patients with NSCLC without AGAs, like EGFR or ALK, most patients eventually experience disease progression. 3-5 TROP2 is a protein expressed in more than 90% of NSCLC tumours; there are currently no TROP2-directed ADCs approved for the treatment of lung cancer. 6-8 Across previously untreated and pretreated patients, an objective response rate (ORR) of 38% was observed (95% confidence interval [CI], 26-51) in patients receiving doublet datopotamab deruxtecan plus pembrolizumab (Merck & Co., Inc., Rahway, NJ, USA), an anti-PD-1 therapy. In patients receiving triplet datopotamab deruxtecan plus pembrolizumab and platinum chemotherapy, an ORR of 49% was observed (95% CI, 37-61). Disease control rates (DCR) of 84% and 87% were observed in the doublet and triplet cohorts, respectively. Median duration of response (DoR) was not reached across cohorts. Although immature, median progression-free survival (PFS) was 8.3 months (95% CI, 6.8-11.8) in the doublet cohort and 7.8 months (95% CI, 5.6-11.1) in the triplet cohort. Response rates were highest in previously untreated patients with ORRs of 50% (95% CI, 32-68) and 57% (95% CI, 42-70) observed in the doublet and triplet cohorts, respectively, with a consistent DCR of 91% observed across cohorts. Yasushi Goto, MD, Division of Internal Medicine and Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan, and investigator in the trial, said: “Nearly all patients with advanced non-small cell lung cancer experience disease progression following initial therapy, underscoring the need for novel therapeutic approaches across treatment lines. The updated results from TROPION-Lung02 signal the potential for datopotamab deruxtecan combinations to improve outcomes for patients with non-small cell lung cancer and are a promising development in the pursuit of a new standard treatment option beyond immunotherapy.” Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: “With more patients and nearly a year of additional follow-up, the updated TROPION-Lung02 results show that datopotamab deruxtecan continues to elicit promising and durable responses in a diverse subset of patients with non-small cell lung cancer. These early data give us confidence in the ongoing Phase III development programme evaluating datopotamab deruxtecan combinations as potential first-line treatment options for patients with advanced lung cancer across tumour histologies and PD-L1 expression levels.” Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo said: “We continue to be encouraged by the findings from TROPION-Lung02, the first trial to evaluate the combination of a TROP2-directed antibody-drug conjugate and an immune checkpoint inhibitor with or without platinum chemotherapy in patients with advanced non-small cell lung cancer. These data, alongside previous results for datopotamab deruxtecan combined with an immune checkpoint inhibitor, reinforce the potential of these combinations to improve outcomes for patients with different advanced cancers.” The safety profiles of datopotamab deruxtecan-based combinations were consistent with previous data with no new safety signals observed. Grade 3 or greater treatment-related adverse events (TRAEs) occurred in 31% of patients receiving doublet therapy and 58% of patients receiving triplet therapy. The most frequent adverse events of any Grade in the doublet and triplet cohorts, respectively, were stomatitis (56% and 35%), nausea (41% and 47%), anaemia (21% and 48%) and fatigue (31% and 37%). Across treatment cohorts, there were 27 interstitial lung disease (ILD) or pneumonitis events adjudicated as drug-related by an independent committee. The percentage of ILD events was similar across cohorts. The majority of ILD events were low grade with 23 Grade 1 or Grade 2 and four Grade 3 events. No Grade 4 or Grade 5 ILD events or Grade 5 TRAEs were observed. In the doublet cohort of TROPION-Lung02, 58% of patients were previously untreated and 42% were previously treated with platinum chemotherapy (38%) or immunotherapy (19%). In the triplet cohort, 75% of patients were previously untreated and 25% were previously treated with platinum chemotherapy (24%) or immunotherapy (25%). Eighty percent of patients in the doublet cohort and 73% of patients in the triplet cohort had PD-L1 tumour proportion scores of less than 50%, including 36% and 40% of patients who had PD-L1 tumour proportion scores of less than 1% in the doublet and triplet cohorts, respectively. As of the April 7, 2023 data cut-off, 36% and 46% of patients remained on the doublet and triplet therapy, respectively. Summary of Results Overall Population Doublet (n=64) Triplet (n=72) Study Duration (range) 14.8 months (1-30.2) 12.9 months (2.6-23.4) Efficacy Measure Doublet (n=61) Triplet (n=71) ORR, % i (confirmed and pending) (95% CI) 38% (n=23) (26-51) 49% (n=35) (37-61) CR, % (confirmed) 0% (n=0) 1% (n=1) CR, % (pending confirmation) 0% (n=0) 0% (n=0) PR, % (confirmed) 34% (n=21) 48% (n=34) PR, % (pending confirmation) 3% (n=2) 0% (n=0) SD, % 49% (n=30) 38% (n=27) Median DoR (months) (95% CI) NR (8.8-NR) NR (5.8-NR) Median PFS (months) (95% CI) 8.3 months (6.8-11.8) 7.8 months (5.6-11.1) DCR, % ii 84% (n=51) 87% (n=62) 1st-Line Therapy Efficacy Measure Doublet (n=34) Triplet (n=53) ORR, % i (confirmed and pending) (95% CI) 50% (n=17) (32-68) 57% (n=30) (42-70) CR, % (confirmed) 0% (n=0) 2% (n=1) CR, % (pending confirmation) 0% (n=0) 0% (n=0) PR, % (confirmed) 44% (n=15) 55% (n=29) PR, % (pending confirmation) 6% (n=2) 0% (n=0) SD, % 47% (n=16) 34% (n=18) Median DoR (months) (95% CI) NR (5.5-NR) NR (5.7-NR) DCR, % ii 91% (n=31) 91% (n=48) CI, confidence interval; CR, complete response; DCR, disease control rate; DoR, duration of response; NR, not reached; ORR, objective response rate; PFS, progression-free survival; PR, partial response; SD, stable disease iORR is CR + PR iiDCR is best overall response of confirmed CR + confirmed PR + SD AstraZeneca and Daiichi Sankyo have three Phase III trials evaluating datopotamab deruxtecan as a potential 1st-line treatment option for patients with advanced or metastatic NSCLC without AGAs compared to the respective standard of care for the patient population of each study: · TROPION-Lung07 is evaluating datopotamab deruxtecan plus pembrolizumab with or without chemotherapy in patients with non-squamous disease and PD-L1 expression less than 50%. · TROPION-Lung08 is evaluating datopotamab deruxtecan plus pembrolizumab in patients with PD-L1 expression of 50% or greater. · AVANZAR is evaluating datopotamab deruxtecan plus Imfinzi (durvalumab) and platinum chemotherapy in patients regardless of PD-L1 expression or tumour histology. Notes Non-small cell lung cancer More than one million people are diagnosed with advanced stage NSCLC each year. 1,2 While targeted therapies and immune checkpoint inhibitors have improved patient outcomes, advanced NSCLC has a poor prognosis and is associated with worsening outcomes after each line of subsequent therapy. 3-5 Most patients with NSCLC have tumours that do not express a known AGA (e.g., EGFR, ALK, ROS1, NTRK, BRAF, RET or MET). 9-11 The current 1st-line standard of care for these patients is treatment with immune checkpoint inhibitors with or without platinum-based chemotherapy. Approximately 40-60% of tumours will not respond to this initial treatment and while these therapies may improve survival for patients whose tumours do respond, most will experience disease progression. 5,7 TROP2, a transmembrane glycoprotein, is expressed in more than 90% of NSCLC tumours. 6 There are currently no TROP2-directed ADCs approved for the treatment of lung cancer. 7,8 TROPION-Lung02 TROPION-Lung02 is an ongoing global, open-label, six-cohort Phase Ib trial evaluating the safety and efficacy of datopotamab deruxtecan at two dose levels (4 mg/kg and 6 mg/kg) in combination with pembrolizumab (200 mg) with or without four cycles of platinum chemotherapy (carboplatin or cisplatin) in both previously untreated and pretreated patients with advanced or metastatic NSCLC without AGAs (e.g., EGFR, ALK, ROS1, NTRK, BRAF, RET, MET or other known AGAs). The primary endpoints of TROPION-Lung02 are dose-limiting toxicities and treatment-emergent adverse events. Secondary endpoints include ORR, DoR, PFS as assessed by investigator, overall survival, pharmacokinetics and anti-drug antibodies for datopotamab deruxtecan and pembrolizumab. TROPION-Lung02 is one of three clinical trials, alongside TROPION-Lung07 and TROPION-Lung08, in a collaboration and supply agreement between Daiichi Sankyo, AstraZeneca and a subsidiary of Merck & Co., Inc., Rahway, NJ., USA to evaluate the combination of datopotamab deruxtecan and pembrolizumab. Datopotamab deruxtecan (Dato-DXd) Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, datopotamab deruxtecan is one of the three lead ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads, an exatecan derivative, via tetrapeptide-based cleavable linkers. A comprehensive development program called TROPION is underway globally with more than 12 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple tumours, including NSCLC, triple-negative breast cancer and hormone-receptor positive, HER2-low or negative breast cancer. Beyond the TROPION programme, datopotamab deruxtecan is also being evaluated in novel combinations in several ongoing trials. Daiichi Sankyo collaboration Daiichi Sankyo Company, Limited (TSE: 4568) [referred to as Daiichi Sankyo] and AstraZeneca entered into a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and datopotamab deruxtecan. AstraZeneca in lung cancer AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most. The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including Tagrisso (osimertinib) and Iressa (gefitinib); Imfinzi (durvalumab) and Imjudo (tremelimumab); Enhertu (trastuzumab deruxtecan) and datopotamab deruxtecan in collaboration with Daiichi Sankyo; Orpathys (savolitinib) in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action. AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment. AstraZeneca in oncology AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience. By harnessing the power of six scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics and Cell Therapies – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death. AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca. References 1. Siegel R, et al . Cancer Statistics, 2021. CA Cancer J Clin . 2021;71:7-33. 2. World Health Organisation. International Agency for Research on Cancer. Available at: https://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf. Accessed June 2023. 3. Shields MD, et al . Immunotherapy for Advanced Non–Small Cell Lung Cancer: A Decade of Progress. Am Soc Clin Oncol Educ Book . 2021;41:1-23. 4. Walsh RJ, et al . Resistance to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer: Biomarkers and Therapeutic Strategies. Ther Adv Med Oncol . 2020;12:1758835920937902. 5. Paz-Ares L, et al . A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous NSCLC: Protocol-Specified Final Analysis of KEYNOTE-407. J Thorac Oncol . 2020;15(10):1657-1669. 6. Mito R, et al . Clinical impact of TROP2 in non‐small lung cancers and its correlation with abnormal p53 nuclear accumulation. Pathol Int . 2020;70(5):287-294. 7. Rodríguez-Abreau D, et al . Pemetrexed Plus Platinum with or without Pembrolizumab in Patients with Previously Untreated Metastatic Nonsquamous NSCLC: Protocol-Specified Final Analysis from KEYNOTE-189. Ann Onc . 2021 Jul;32(7): 881-895. 8. American Cancer Society. Targeted Drug Therapy for Non-Small Cell Lung Cancer. Available at: https://www.cancer.org/cancer/types/lung-cancer/treating-non-small-cell/targeted-therapies.html. Accessed June 2023. 9. Chen R, et al . Emerging Therapeutic Agents for Advanced Non-Small Cell Lung Cancer. J Hematol Oncol . 2020;13(1):58. 10. Majeed U, et al . Targeted therapy in advanced non-small cell lung cancer: current advances and future trends. J Hematol Oncol . 2021; 14(1): 108. 11. Adib E, et al . Variation in Targetable Genomic Alterations in Non-Small Cell Lung Cancer by Genetic Ancestry, Sex, Smoking History, And Histology. Genome Med . 2022; 14(1): 39. Source: AstraZeneca Posted: June 2023

-- Breadth of pipeline featured in multiple early clinical data presentations, reflecting diversity of fundamental growth drivers across development programs -- CAMBRIDGE, Mass., June 3, 2023 /PRNewswire/ -- Blueprint Medicines Corporation (Nasdaq: BPMC) today announced clinical data for multiple programs across its precision therapy portfolio at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. The presentations showcase the company's progress in developing precision therapies to address the needs of broad patient populations, including hormone-receptor-positive/HER2-negative (HR+/HER2-) breast cancer and EGFR-mutant non-small cell lung cancer (NSCLC). "At ASCO, we are reporting early clinical data for three therapeutic candidates highlighting the breadth of our pipeline, which lays the foundation for our next wave of precision therapy programs to tackle significant medical challenges," said Becker Hewes, M.D., Chief Medical Officer at Blueprint Medicines. "Together, these presentations reflect how we are developing differentiated, highly selective therapies against promising disease targets, and demonstrate strong execution in advancing potential treatment options for large patient populations, including HR+/HER2- breast cancer and EGFR-mutant lung cancer. The datasets represent a diversity of fundamental value drivers in our clinical portfolio, which create opportunities to substantially expand our patient impact and highlight our ambition to deliver many more transformational medicines to patients in the future." CDK2 Program CDK2 is a cell cycle regulator and important cancer target across a broad range of malignancies, including HR+/HER2- breast cancer. Based on the underlying science on the role of CDK2 inhibition in cancer, and the potential for this mechanism to impact large populations of patients, BLU-222 represents one of the most important programs within Blueprint Medicines' early clinical development pipeline. The data reported at ASCO begin to demonstrate the clinical profile of BLU-222, a highly selective and potent oral CDK2 inhibitor. VELA trial: BLU-222 in HR+/HER2- metastatic breast cancer and other advanced cancers Abstract number: 3095 Presentation location and time: Hall A; Saturday, June 3 from 8:00 a.m. — 11:00 a.m. CT Results from the ongoing dose escalation part of the VELA trial of BLU-222 (n=27) showed encouraging safety and evidence of cell cycle pathway modulation consistent with the treatment's best-in-class preclinical profile. Based on these data, Blueprint Medicines is continuing monotherapy dose escalation to identify a maximum tolerated dose, and has initiated dose escalation of BLU-222 in combination with the CDK4/6 inhibitor, ribociclib, and the estrogen receptor antagonist, fulvestrant, in patients with HR+/HER2- metastatic breast cancer. BLU-222 was generally well-tolerated with no discontinuations due to adverse events (AEs). Treatment-related hematologic AEs commonly seen with CDK4/6 inhibitors were generally mild and primarily reported in patients with a history of low blood cell counts. No cardiac AEs or QTc prolongation were observed. BLU-222 showed evidence of cell cycle pathway modulation as demonstrated by circulating and tumor tissue-based biomarker data. Increased BLU-222 doses led to robust reductions in thymidine kinase 1 (TK1) activity and phosphorylated retinoblastoma (pRB). In addition, the presentation highlighted a confirmed partial response in a BLU-222 monotherapy-treated patient with HR+/HER2- metastatic breast cancer who previously received five lines of therapy, including the CDK4/6 inhibitors palbociclib and abemaciclib. EGFR Programs EGFR represents one of the most common oncogenic drivers in NSCLC, and Blueprint Medicines is developing a portfolio of investigational precision therapies to inhibit the broad spectrum of EGFR activating and resistance mutations. With three novel EGFR inhibitors, the company seeks to transform treatment options for patients with EGFR-mutant NSCLC, including with highly active, well-tolerated combinations in the front-line setting. Data reported at ASCO feature two of the company's investigational EGFR inhibitors: BLU-451, a wildtype-EGFR-sparing, CNS-penetrant oral inhibitor of EGFR exon 20 insertions and atypical mutations with best-in-class potential BLU-945, a potent oral EGFR inhibitor designed to be highly selective over wildtype EGFR, supporting its potential as a differentiated combination partner CONCERTO trial: BLU-451 in advanced NSCLC driven by EGFR exon 20 insertions or atypical mutations Abstract number: 9064 Presentation location and time: Hall A; Sunday, June 4 from 8:00 a.m. — 11:00 a.m. CT Results from the ongoing dose escalation part of the CONCERTO trial of BLU-451 in heavily pretreated patients with NSCLC driven by EGFR exon 20 insertions (n=48) or atypical mutations (n=9) showed evidence of safety and clinical benefits, including central nervous system (CNS) activity. The data support continued dose escalation to determine the recommended Phase 2 dose (RP2D), and further development in patients with EGFR exon 20 insertions as well as additional patients with atypical EGFR mutations. Collectively, these mutations represent approximately 20 percent of EGFR-mutant NSCLC cases. BLU-451 was generally well-tolerated in patients, with no grade 3 or higher AEs associated with wildtype EGFR inhibition, no dose-limiting toxicities and no discontinuations due to treatment-related AEs. In patients with EGFR exon 20 insertion-positive NSCLC, BLU-451 demonstrated evidence of clinical activity including circulating tumor DNA (ctDNA) clearance, tumor reductions including confirmed partial responses, and CNS activity. Multiple patients showed CNS benefits including one who had a partial CNS response per RECIST version 1.1 criteria and one who had a CNS complete response with resolution of multiple non-target brain lesions, as highlighted by patient vignettes in the presentation. In patients with NSCLC driven by atypical EGFR mutations, BLU-451 showed emerging dose-dependent ctDNA clearance and tumor shrinkage, reflecting an expanded development opportunity. SYMPHONY trial: BLU-945 monotherapy and in combination with osimertinib in late-line, EGFR-mutant NSCLC Abstract number: 9011 Presentation location and time: S406; Monday, June 5 from 11:30 a.m. — 12:30 p.m. CT Updated results from the dose escalation part of the SYMPHONY trial showed the safety and clinical activity of BLU-945 as a monotherapy (n=112) and in combination with osimertinib (n=55) in patients with late-line, osimertinib-refractory, EGFR-mutant NSCLC. Based on the unprecedented and favorable safety profile for the combination of BLU-945 and osimertinib observed to-date, dose escalation is continuing which impacts the timeframe to establish the RP2D and begin the randomized, first-line treatment portion of the study. Consequently, the company no longer anticipates presenting initial dose expansion data for BLU-945 in combination with osimertinib in first-line, EGFR L858R-positive NSCLC by the end of 2023. BLU-945, as a monotherapy and in combination with osimertinib, was generally well-tolerated, and AEs associated with wildtype EGFR inhibition were infrequent, with the majority reported as Grade 1. For the combination, the discontinuation rate due to treatment-related AEs was 3.6 percent. BLU-945 monotherapy and the combination showed evidence of clinical activity, with ctDNA clearance and tumor reductions including confirmed partial responses observed in patients whose tumors had progressed following treatment with osimertinib. For combination regimens with a total BLU-945 daily dose of 300 mg or higher, tumor shrinkage was observed in 51 percent of patients with molecularly heterogenous, osimertinib-refractory, late-line EGFR-mutant NSCLC, with multiple confirmed responses. Copies of Blueprint Medicines data presentations from the ASCO Annual Meeting are available in the "Science—Publications and Presentations" section of the company's website at . About Blueprint Medicines Blueprint Medicines is a global precision therapy company that invents life-changing therapies for people with cancer and blood disorders. Applying an approach that is both precise and agile, we create medicines that selectively target genetic drivers, with the goal of staying one step ahead across stages of disease. Since 2011, we have leveraged our research platform, including expertise in molecular targeting and world-class drug design capabilities, to rapidly and reproducibly translate science into a broad pipeline of precision therapies. Today, we are delivering our approved medicines to patients in the United States and Europe, and we are globally advancing multiple programs for systemic mastocytosis, lung cancer, breast cancer and other genomically defined cancers, and cancer immunotherapy. For more information, visit and follow us on Twitter (@BlueprintMeds) and LinkedIn. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding Blueprint Medicines' views with respect to its ability to expand its patient impact and deliver more transformational medicines to patients; the potential benefits of Blueprint Medicines' current and future approved drugs or drug candidates in treating patients; and Blueprint Medicines' strategy, goals and anticipated milestones, business plans and focus. The words "aim," "may," "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," "estimate," "predict," "project," "potential," "continue," "target" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks and uncertainties related to our ability and plans in continuing to expand Blueprint Medicines' commercial infrastructure, and successfully launching, marketing and selling current or future approved products; Blueprint Medicines' ability to successfully expand the approved indications for AYVAKIT/AYVAKYT or obtain marketing approval for AYVAKIT/AYVAKYT in additional geographies in the future; the delay of any current or planned clinical trials or the development of our current or future drug candidates; Blueprint Medicines' advancement of multiple early-stage efforts; Blueprint Medicines' ability to successfully demonstrate the safety and efficacy of its drug candidates and gain approval of its drug candidates on a timely basis, if at all; the preclinical and clinical results for Blueprint Medicines' drug candidates, which may not support further development of such drug candidates either as monotherapies or in combination with other agents or may impact the anticipated timing of data or regulatory submissions; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials; Blueprint Medicines' ability to obtain, maintain and enforce patent and other intellectual property protection for its products or any drug candidates it is developing; Blueprint Medicines' ability to develop and commercialize companion diagnostic tests for its products or any of its current and future drug candidates; Blueprint Medicines' ability to successfully expand its research platform and the costs thereof; and the success of Blueprint Medicines' current and future collaborations, partnerships or licensing arrangements. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in Blueprint Medicines' filings with the Securities and Exchange Commission (SEC), including its Annual Report on Form 10-K for the year ended December 31, 2022, as filed with the SEC on February 16, 2023, and any other filings that Blueprint Medicines has made or may make with the SEC in the future. Any forward-looking statements contained in this press release represent Blueprint Medicines' views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, Blueprint Medicines assumes no obligation to update or revise these forward-looking statements for any reason, even if new information becomes available in the future. Trademarks Blueprint Medicines, AYVAKIT, AYVAKYT and associated logos are trademarks of Blueprint Medicines Corporation. SOURCE Blueprint Medicines Corporation