Indolent systemic mastocytosis

-- AYVAKIT data in patients with indolent systemic mastocytosis show durable efficacy and favorable safety supporting long-term treatment, consistent with real-world experience observed in commercial setting -- -- Preclinical data for BLU-808, a highly selective and potent oral wild-type KIT inhibitor with best-in-class potential, supports development in chronic urticaria and other mast cell diseases; on track to submit IND to FDA in Q2 2024 -- -- Breadth of data across 9 presentations, including 2 oral, highlight scientific and clinical leadership -- CAMBRIDGE, Mass., Feb. 23, 2024 /PRNewswire/ -- Blueprint Medicines Corporation (Nasdaq: BPMC) today announced PIONEER trial results highlighting the long-term efficacy and safety of AYVAKIT® (avapritinib) in patients with indolent systemic mastocytosis (ISM), as well as foundational preclinical data for BLU-808, an investigational highly selective and potent oral inhibitor of wild-type KIT. Blueprint Medicines will report a total of nine data presentations, including two oral presentations, reflecting the company's long-standing commitment to transform care for patients living with mast cell disorders. The datasets are being reported at the 2024 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting being held February 23-26 in Washington, D.C. "PIONEER data show that long-term treatment with AYVAKIT led to robust and durable clinical efficacy across a wide range of symptoms, and a well-tolerated safety profile that has remained remarkably consistent over time," said Becker Hewes, M.D., Chief Medical Officer at Blueprint Medicines. "These compelling long-term data, combined with the real-world experience of more than a thousand patients currently on therapy in the U.S., indicate our continued momentum in establishing AYVAKIT as a new standard of care for patients living with ISM. With an SM franchise anchored by AYVAKIT, and the opportunity to expand and extend our reach with elenestinib, Blueprint Medicines is transforming treatment across the spectrum of the disease and redefining what well-controlled means for patients." AYVAKIT: Durable Symptom Impact and Well-Tolerated Safety Profile in Patients with ISM Long-term data from the PIONEER trial show that AYVAKIT led to robust improvements across all symptom domains (skin, gastrointestinal, neurocognitive) at 24 weeks, with sustained benefits through 48 weeks. In addition, patients treated with placebo during the blinded portion of the trial had rapid and durable symptom improvements upon cross-over to AYVAKIT. Symptom improvements were assessed by the validated Indolent Systemic Mastocytosis Symptom Assessment Form (ISM-SAF). After 48 weeks of treatment with AYVAKIT, 35 percent of patients reduced or discontinued use of best supportive care medicines. As of the updated data cut, the last patient treated with AYVAKIT in the blinded portion of the trial reached the 48-week timepoint. With a median patient follow-up of 18 months, the safety profile of AYVAKIT was consistent with previously reported results from the 6-month placebo-controlled portion of the trial, with no new safety signals observed. Most adverse events (AEs) were mild or moderate (Grade 1-2), and the most common treatment-related AEs (≥5 percent) were peripheral edema, headache, periorbital edema and nausea. The rate of treatment-related AEs leading to discontinuation remained low (3 percent). BLU-808: An Investigational, Potent and Selective Wild-type KIT Inhibitor for Chronic Urticaria and Other Mast Cell Diseases Mast cells play a critical frontline role in a healthy immune response; activation through KIT and other receptors leads to degranulation and release of downstream effectors that mediate inflammation. However, when mast cells are dysregulated, they are drivers of multiple common allergic and inflammatory diseases such as chronic urticaria, for which wild-type KIT is a clinically validated therapeutic target. BLU-808 is an investigational, highly selective and potent oral wild-type KIT inhibitor designed to enable tolerability and flexibility to tailor treatment based on disease severity and patient needs. "The development of BLU-808 is another example of our proven track record of designing exquisitely selective molecules that inhibit important biologic targets. Specifically, our scientists engineered BLU-808 to potently target wild-type KIT, while maintaining a wide therapeutic index conducive to chronic treatment," said Percy Carter, Ph.D., Chief Scientific Officer at Blueprint Medicines. "The BLU-808 program highlights our focused efforts to scale our science in allergy/inflammation, leveraging our expertise in mast cell biology and fully integrated R&D and commercial capabilities. By targeting the root cause of a variety of inflammatory diseases, BLU-808 represents a potential best-in-class mast cell modulator that may benefit large patient populations with high medical needs." In foundational preclinical data reported at AAAAI, BLU-808 demonstrated a best-in-class selectivity and potency profile in vitro. In multiple in vivo studies, BLU-808 treatment led to dose-dependent inhibition and depletion of mast cells. In addition, BLU-808 improved lung function in an ovalbumin-induced asthma model. Based on these data, Blueprint Medicines expects to submit an investigational new drug application for BLU-808 in the second quarter of 2024, and subsequently plans to initiate a Phase 1 study in healthy volunteers. The initial development focus for BLU-808 will be in chronic urticaria. Blueprint Medicines' AAAAI data presentations are listed below. Copies of the data presentations are available in the "Science—Publications and Presentations" section of the company's website at . Data Presentations Presentation Title: BLU-808, a Potent and Selective Small Molecule Inhibitor of Wild-type c-KIT for Mast Cell Disorders Session Title: Novel Treatment Approaches in Allergic Disease, Poster Session Session Date & Time: Friday, February 23 from 3:15 – 4:15 p.m. ET Abstract Number: 189 Location: Convention Center, Level 2, Hall D Presentation Title: Patient-Reported Outcome Measures in Systemic Mastocytosis: A Systematic Review Session Title: Mast Cell Disorders, Poster Session Session Date & Time: Sunday, February 25 from 9:45 – 10:45 a.m. ET Abstract Number: 689 Location: Convention Center, Level 2, Hall D Presentation Title: Reductions in Polypharmacy for Patients with Indolent Systemic Mastocytosis on Avapritinib Session Title: Mast Cell Disorders, Poster Session Session Date & Time: Sunday, February 25 from 9:45 – 10:45 a.m. ET Abstract Number: 696 Location: Convention Center, Level 2, Hall D Presentation Title: Systemic Mastocytosis: Shedding Light on a Rare and Complicated Disease Session Title: Mast Cell Disorders, Poster Session Session Date & Time: Sunday, February 25 from 9:45 – 10:45 a.m. ET Abstract Number: 691 Location: Convention Center, Level 2, Hall D Presentation Title: The Five Dimensions of the ISM Patient Experience – Uncovering the "Real-world" Experience of Patients with Indolent Systemic Mastocytosis Session Title: Mast Cell Disorders, Poster Session Session Date & Time: Sunday, February 25 from 9:45 – 10:45 a.m. ET Abstract Number: 693 Location: Convention Center, Level 2, Hall D Presentation Title: Quantifying Diagnostic Delays in Patients with Indolent and Aggressive Systemic Mastocytosis Session Title: Mast Cell Disorders, Poster Session Session Date & Time: Sunday, February 25 from 9:45 – 10:45 a.m. ET Abstract Number: 692 Location: Convention Center, Level 2, Hall D Oral Presentation Title: Exploring the Spectrum of Indolent Systemic Mastocytosis: Analysis of High-Risk Disease Features in the PIONEER Study Session Title: Mast Cell Disorders: Bench to Bedside, Oral Abstract Session Session Date & Time: Sunday, February 25 from 2:15 – 2:25 p.m. ET Abstract Number: 737 Location: Convention Center, Level 1, Room 144B Oral Presentation Title: Prevalence of The KIT D816V Mutation In Peripheral Blood (PB) of Patients With Evidence of Systemic Mast Cell Activation (MCA): Results of The Prospective, Multi-centered, Global PROSPECTOR Clinical Trial Session Title: Mast Cell Disorders: Bench to Bedside, Oral Abstract Session Session Date & Time: Sunday, February 25 from 2:25 – 2:35 p.m. ET Abstract Number: 739 Location: Convention Center, Level 1, Room 144B Presentation Title: Avapritinib Decreased Symptom Burden in Patients with Indolent Systemic Mastocytosis in the Registrational Double-Blind, Placebo-Controlled PIONEER Study Session Title: Novel Cellular and Molecular Pathways of Allergic Inflammation, Featured Poster Session Session Date & Time: Sunday, February 25 from 4:45 – 6:15 p.m. ET Abstract Number: 783 Location: Convention Center, Level 3, Ballroom South Prefunction About Systemic Mastocytosis Systemic mastocytosis (SM) is a rare disease driven by the KIT D816V mutation in about 95 percent of cases. Uncontrolled proliferation and activation of mast cells result in chronic, severe and often unpredictable symptoms across multiple organ systems. The vast majority of those affected have indolent systemic mastocytosis (ISM). A broad range of symptoms, including anaphylaxis, maculopapular rash, pruritis, diarrhea, brain fog, fatigue and bone pain, frequently persist in patients with ISM despite treatment with multiple symptom-directed therapies. This burden of disease can lead to a profound, negative impact on quality of life. Patients often live in fear of severe, unexpected symptoms, have limited ability to work or perform daily activities, and isolate themselves to protect against unpredictable triggers. Historically, there had been no approved therapies for the treatment of ISM. A minority of patients have advanced SM, which encompasses a group of high-risk SM subtypes including ASM, SM-AHN and MCL. In addition to mast cell activation symptoms, advanced SM is associated with organ damage due to mast cell infiltration and poor survival. About AYVAKIT (avapritinib) AYVAKIT (avapritinib) is approved by the U.S. Food and Drug Administration (FDA) for the treatment of three indications: adults with ISM, adults with advanced SM, including aggressive SM (ASM), SM with an associated hematological neoplasm (SM-AHN) and mast cell leukemia (MCL), and adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. For more information, visit AYVAKIT.com. This medicine is approved by the European Commission (AYVAKYT®) for the treatment of adults with ASM, SM-AHN or MCL, after at least one systemic therapy, and adults with unresectable or metastatic GIST harboring the PDGFRA D842V mutation. Please click here to see the full U.S. Prescribing Information for AYVAKIT, and click here to see the European Summary of Product Characteristics for AYVAKYT. To learn about ongoing or planned clinical trials, contact Blueprint Medicines at [email protected] or 1-888-BLU-PRNT (1-888-258-7768). Additional information is available at blueprintclinicaltrials.com or clinicaltrials.gov. Important Safety Information Intracranial Hemorrhage—Serious intracranial hemorrhage (ICH) may occur with AYVAKIT treatment; fatal events occurred in <1% of patients. Overall, ICH (eg, subdural hematoma, ICH, and cerebral hemorrhage) occurred in 2.9% of 749 patients who received AYVAKIT in clinical trials. In Advanced SM patients who received AYVAKIT at 200 mg daily, ICH occurred in 2 of 75 patients (2.7%) who had platelet counts ≥50 x 109/L prior to initiation of therapy and in 3 of 80 patients (3.8%) regardless of platelet counts. In ISM patients, no events of ICH occurred in the 246 patients who received any dose of AYVAKIT in the PIONEER study. Monitor patients closely for risk factors of ICH, which may include history of vascular aneurysm, ICH or cerebrovascular accident within the prior year, concomitant use of anticoagulant drugs, or thrombocytopenia. Symptoms of ICH may include headache, nausea, vomiting, vision changes, or altered mental status. Advise patients to seek immediate medical attention for signs or symptoms of ICH. Permanently discontinue AYVAKIT if ICH of any grade occurs. In Advanced SM patients, a platelet count must be performed prior to initiating therapy. AYVAKIT is not recommended in Advanced SM patients with platelet counts <50 x 109/L. Following treatment initiation, platelet counts must be performed every 2 weeks for the first 8 weeks. After 8 weeks of treatment, monitor platelet counts every 2 weeks or as clinically indicated based on platelet counts. Manage platelet counts of <50 x 109/L by treatment interruption or dose reduction. Cognitive Effects—Cognitive adverse reactions can occur in patients receiving AYVAKIT and occurred in 33% of 995 patients overall in patients who received AYVAKIT in clinical trials including: 28% of 148 Advanced SM patients (3% were Grade ≥3), and 7.8% of patients with ISM who received AYVAKIT + best supportive care (BSC) versus 7.0% of patients who received placebo + BSC (<1% were Grade 3). Depending on the severity and indication, withhold AYVAKIT and then resume at same dose or at a reduced dose upon improvement, or permanently discontinue. Photosensitivity—AYVAKIT may cause photosensitivity reactions. In all patients treated with AYVAKIT in clinical trials (n=1049), photosensitivity reactions occurred in 2.5% of patients. Advise patients to limit direct ultraviolet exposure during treatment with AYVAKIT and for one week after discontinuation of treatment. Embryo-Fetal Toxicity—AYVAKIT can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use an effective method of contraception during treatment with AYVAKIT and for 6 weeks after the final dose of AYVAKIT. Advise women not to breastfeed during treatment with AYVAKIT and for 2 weeks after the final dose. Adverse Reactions—The most common adverse reactions (≥20%) in patients with Advanced SM were edema, diarrhea, nausea, and fatigue/asthenia. The most common adverse reactions (≥10%) in patients with ISM were eye edema, dizziness, peripheral edema, and flushing. Drug Interactions—Avoid coadministration of AYVAKIT with strong or moderate CYP3A inhibitors. If coadministration with a moderate CYP3A inhibitor cannot be avoided in patients with Advanced SM, reduce dose of AYVAKIT. Avoid coadministration of AYVAKIT with strong or moderate CYP3A inducers. To report suspected adverse reactions, contact Blueprint Medicines Corporation at 1-888-258-7768 or FDA at 1-800-FDA-1088 or . Please click here to see the full Prescribing Information for AYVAKIT. About Blueprint Medicines Blueprint Medicines is a fully integrated, commercial-stage, global biopharmaceutical company that invents life-changing medicines in two core, strategic areas of allergy/inflammation and oncology/hematology. We pursue discovery, development, and commercialization of therapies that potently and selectively target known drivers of disease, with focused investment in therapeutic areas where we can leverage our core expertise and business infrastructure to bring scale to our science. We are bringing AYVAKIT®/AYVAKYT® (avapritinib) to people living with systemic mastocytosis (SM) in the U.S. and Europe. Additionally, we have a pipeline of research and development programs that range from early science to advanced clinical trials in mast cell-mediated diseases, including SM and chronic urticaria, breast cancer, and other solid tumors vulnerable to CDK2 inhibition. For more information, visit and follow us on X (formerly 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 expectations for the potential benefits of AYVAKIT in treating patients with ISM; Blueprint Medicines' ability to transform treatment across the spectrum of SM; the development of BLU-808 and whether it has best-in-class potential; plans and timing for submitting an IND to the FDA for BLU-808; statements regarding plans and expectations for Blueprint Medicines' current or future approved drugs and drug candidates; the potential benefits of any of Blueprint Medicines' current or future approved drugs or drug candidates in treating patients; and Blueprint Medicines' strategy, goals, 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 Blueprint Medicines' ability and plans in continuing to build out and expand a 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 Blueprint Medicines' 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; the timing of the initiation of clinical trials and trial cohorts at clinical trial sites and patient enrollment rates; 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 AYVAKIT/AYVAKYT or any drug candidates it is developing; Blueprint Medicines' ability to successfully expand its operations, research platform and portfolio of therapeutic candidates, and the timing and costs thereof; and the success of Blueprint Medicines' current and future collaborations, financing arrangements, 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 Blueprint Medicines' most recent Annual Report on Form 10-K, as supplemented by its most recent Quarterly Report on Form 10-Q 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 explicitly disclaims any obligation to update any forward-looking statements. Trademarks Blueprint Medicines, AYVAKIT, AYVAKYT and associated logos are trademarks of Blueprint Medicines Corporation. SOURCE Blueprint Medicines Corporation

-- Achieved $204.2 million in AYVAKIT®/AYVAKYT® (avapritinib) net product revenues in 2023, including $71.0 million in the fourth quarter -- -- Anticipate global AYVAKIT net product revenue of approximately $360 million to $390 million in 2024, representing >80 percent year-over-year growth at the midpoint -- -- Nine presentations highlighting AYVAKIT long-term safety and efficacy, BLU-808 preclinical profile, and additional data fortifying leadership in mast cell diseases accepted for presentation at 2024 AAAAI Annual Meeting -- CAMBRIDGE, Mass., Feb. 15, 2024 /PRNewswire/ -- Blueprint Medicines Corporation (NASDAQ: BPMC) today reported financial results and provided a business update for the fourth quarter and full year ended December 31, 2023 and provided financial guidance. "As we enter 2024, AVAYKIT continues to be the foundation of our thriving and growing commercial business. Our 2024 guidance of $360 to $390 million sets us up to nearly double AYVAKIT product revenue this year, driven by the launch in ISM as we focus on reaching more patients in both the U.S. and Europe. AYVAKIT's compelling efficacy and safety profile, coupled with the chronic nature of ISM, make the cumulative effect of patients staying on therapy an important revenue driver this year, beyond and in addition to new patient starts. AYVAKIT is firmly on the path to becoming a multibillion-dollar product, providing Blueprint with durable revenue growth well into the next decade. Beyond AYVAKIT and ISM, we are balancing investment in our most compelling pipeline opportunities and maintaining financial discipline, strengthening our financial profile, and accelerating our path to profitability," said Kate Haviland, Chief Executive Officer of Blueprint Medicines. "We are particularly excited about our expanding portfolio targeting allergic-inflammatory diseases where mast cells play a central role, and we are looking forward to sharing more on these programs throughout this year." Fourth Quarter 2023 Highlights and Recent Progress Mast cell disorders Achieved AYVAKIT net product revenues of $204.2 million and $71.0 million for the full year and the fourth quarter of 2023, respectively, representing 84 percent growth year-over-year. Announced approval by the European Commission for AYVAKYT as the first and only treatment for indolent systemic mastocytosis (ISM). Read the press release here. Presented data demonstrating the compelling benefit-risk profile of elenestinib in ISM from Part 1 of the HARBOR trial and analyses of real-world data highlighting the burden of and urgency to treat ISM at the 2023 American Society of Hematology annual meeting. Read the presentations here. Breast cancer and other solid tumors Advanced the development of BLU-222 in combination with ribociclib and fulvestrant in patients with HR+/HER2- breast cancer. Announced the development candidate nomination of BLU-956, a next-generation CDK2 inhibitor. Corporate Presented a 2024 corporate overview and strategy at the J.P. Morgan 42nd Annual Healthcare Conference. Read the press release here. Identified an alternate partner for GAVRETO® (pralsetinib) in the U.S. and are working with all involved parties to enable continuity of access to GAVRETO in the U.S. The company plans to provide an update to coincide with the late February 2024 termination date of the existing collaboration agreement with Roche. The company continues to expect that the wind-down of the Roche collaboration for GAVRETO and the discontinuation of global development and marketing in territories outside the U.S. and Greater China will result in significantly lower year-over-year operating expenses related to GAVRETO and will have no material impact to its overall operating expense plans in 2024. 2024 Financial Guidance Blueprint Medicines today announced it anticipates approximately $360 million to $390 million in global AYVAKIT net product revenues for all approved indications in 2024. The midpoint of this range represents more than 80 percent year-over-year revenue growth, the majority of which is expected to be driven by ISM. The company continues to expect that operating expenses and cash burn will further decline in 2024, and that its existing cash, cash equivalents and investments, together with anticipated future product revenues, will maintain a durable capital position to enable the company to achieve a self-sustainable financial profile. Key Upcoming Milestones The company plans to achieve the following milestones in the first half of 2024: Mast cell diseases Present long-term safety and efficacy data from the PIONEER trial of AYVAKIT in ISM at the 2024 American Academy of Allergy, Asthma and Immunology (AAAAI) Annual Meeting. Present preclinical data for BLU-808, a highly selective and potent oral inhibitor of wild-type KIT, at the 2024 AAAAI Annual Meeting. Submit an investigational new drug application for BLU-808 in the second quarter of 2024. Breast cancer and other solid tumors Continue ongoing strategic business development discussions. Present data for BLU-222 in combination with ribociclib and fulvestrant in patients with HR+/HER2- breast cancer in the first half of 2024. Fourth Quarter and Year End 2023 Results Revenues: Revenues were $72.0 million for the fourth quarter of 2023, including $71.0 million of net product revenues from sales of AYVAKIT/AYVAKYT and $0.9 million in collaboration revenues. Revenues for the year ended December 31, 2023 were $249.4 million, including $204.2 million of net product revenues from sales of AYVAKIT/AYVAKYT, and $45.2 million in collaboration and license revenues. Blueprint Medicines recorded $38.8 million and $204.0 million in revenues in the fourth quarter and year ended December 31, 2022, respectively. Cost of Sales: Cost of sales was $0.3 million for the fourth quarter of 2023 and $8.5 million for the year ended December 31, 2023, as compared to $4.8 million and $17.8 million for the fourth quarter and year ended December 31, 2022, respectively. This decrease was mainly due to a decrease in inventory write-downs and the cost of collaboration-related sales. R&D Expenses: Research and development expenses were $97.5 million for the fourth quarter of 2023 and $427.7 million for the year ended December 31, 2023, as compared to $117.8 million and $477.4 million for the fourth quarter and year ended December 31, 2022, respectively. This decrease was primarily due to a focused approach towards optimizing operational efficiency across Blueprint Medicine's portfolio as the company executes across its top priority programs and the timing of manufacturing of clinical trial materials. Research and development expenses also included $10.0 million in stock-based compensation expenses for the fourth quarter of 2023 and $41.5 million in stock-based compensation for the year ended December 31, 2023. SG&A Expenses: Selling, general and administrative expenses were $79.3 million for the fourth quarter of 2023 and $295.1 million for the year ended December 31, 2023, as compared to $64.0 million and $237.4 million for the fourth and year ended December 31, 2022, respectively. This increase was primarily due to an increase in compensation and personnel related costs driven by the company's first quarter 2023 field force expansion to support the AYVAKIT launch in ISM and an increase in commercial and related activities primarily related to the commercialization of AYVAKIT/AYVAKYT. Selling, general and administrative expenses included $12.6 million in stock-based compensation expenses for the fourth quarter of 2023 and $51.1 million in stock-based compensation for the year ended December 31, 2023. Net Income (Loss): Net loss was $(110.9) million for the fourth quarter of 2023 and $(507.0) million for the year ended December 31, 2023, or a diluted net loss per share of $(1.82) and diluted net loss per share of $(8.37), respectively, as compared to a net loss of $(158.6) million for the fourth quarter of 2022 and a net loss of $(557.5) million for the year ended December 31, 2022, or a diluted net loss per share of $(2.65) and a diluted net loss per share of $(9.35), respectively. Cash Position: As of December 31, 2023, cash, cash equivalents and marketable securities were $767.2 million, as compared to $1,078.5 million as of December 31, 2022. Blueprint Medicine's cash and investments provide a durable capital position which enables the company to reach a self-sustainable profile. Conference Call Information Blueprint Medicines will host a live conference call and webcast at 8:00 a.m. ET today to discuss fourth quarter and full year 2023 financial results and recent business activities. The conference call may be accessed by dialing 833-470-1428 (domestic) or 404-975-4839 (international), and referring to conference ID 071930. A webcast of the call will also be available under "Events and Presentations" in the Investors & Media section of the Blueprint Medicines website at . The archived webcast will be available on Blueprint Medicines' website approximately two hours after the conference call and will be available for 30 days following the call. Upcoming Investor Conferences Blueprint Medicines will participate in one upcoming investor conference: Cowen 44th Annual Health Care Conference on Monday, March 4, 2024 at 9:10 am ET. A live webcast of the presentation will be available under "Events and Presentations" in the Investors & Media section of the Blueprint Medicines website at . A replay of the webcast will be archived on the Blueprint Medicines website for 30 days following the presentation. About Blueprint Medicines Blueprint Medicines is a fully-integrated, commercial-stage, global biopharmaceutical company that invents life-changing medicines in two core, strategic areas of allergy/inflammation and oncology/hematology. We pursue discovery, development, and commercialization of therapies that potently and selectively target known drivers of disease, with focused investment in therapeutic areas where we can leverage our core expertise and business infrastructure to bring scale to our science. We are bringing AYVAKIT®/AYVAKYT® (avapritinib) to people living with systemic mastocytosis (SM) in the U.S. and Europe. Additionally, we have a pipeline of research and development programs that range from early science to advanced clinical trials in mast cell-mediated diseases, including SM and chronic urticaria, breast cancer, and other solid tumors vulnerable to CDK2 inhibition. For more information, visit and follow us on X (formerly 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 plans, strategies, timelines and expectations for Blueprint Medicines' future business growth, including its expectations for growth in 2024; AYVAKIT's potential as a blockbuster market opportunity in SM; whether the any of Blueprint Medicines' product candidates will address unmet medical needs; reduction of the Blueprint Medicines' operating expenses and cash burn in 2024; statements regarding plans and expectations for the company's current or future approved drugs and drug candidates; the potential benefits of any of the Blueprint Medicines' current or future approved drugs or drug candidates in treating patients; and the Blueprint Medicines' financial performance, 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: the risk of delay of any current or planned clinical trials or the development of Blueprint Medicines' current or future drug candidates; risks related to 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; preclinical and clinical results for Blueprint Medicines' drug candidates 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; the timing of the initiation of clinical trials and trial cohorts at clinical trial sites and patient enrollment rates may be delayed or slower than anticipated; actions of regulatory agencies may affect the initiation, timing and progress of clinical trials; risks related to Blueprint Medicines' ability to obtain, maintain and enforce patent and other intellectual property protection for its products and current or future drug candidates it is developing; and the success of Blueprint Medicines' current and future collaborations, financing arrangements, partnerships or licensing arrangements. 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 explicitly disclaims any obligation to update any forward-looking statements. Trademarks Blueprint Medicines, AYVAKIT, AYVAKYT, GAVRETO and associated logos are trademarks of Blueprint Medicines Corporation. SOURCE Blueprint Medicines Corporation

The European Commission (EC) has approved Blueprint Medicines’ Ayvakyt (avapritinib) as the first treatment for indolent systemic mastocytosis (ISM). Systemic mastocytosis (SM) is a rare haematological disorder that can lead to a range of debilitating symptoms across multiple organ systems. ISM accounts for the vast majority of SM cases and, despite the availability of multiple symptom-directed therapies, a number of ISM patients continue to experience a substantial disease burden. Blueprint’s Ayvakyt works by targeting KIT D816V, the primary underlying cause of the disease. “Ayvakyt represents an important treatment breakthrough as the first medicine approved for patients living with ISM, and the only therapy designed to selectively target the primary genetic driver of the disease,” said Jens Panse, deputy director of the department of haematology/oncology at the University Hospital RWTH Aachen in Germany. The EC’s decision on the drug follows a recent recommendation from the European Medicines Agency’s human medicines committee and was supported by positive results from the PIONEER trial, the largest study ever conducted in ISM. Results showed that Ayvakyt was associated with significant improvements versus placebo in the primary and all key secondary endpoints, including overall symptoms and measures of mast cell burden. Ayvakyt was also found to be well-tolerated with a favourable safety profile, and most adverse reactions were reported as mild. “Based on this practice-changing data, Ayvakyt has the potential to advance treatment for a broad range of patients living with ISM,” Panse said. Georg Pirmin Meyer, senior vice president, international at Blueprint Medicines, said the approval "represents an important step toward delivering a new global standard of care for patients with ISM”. "For the first time in Europe, ISM patients have an approved therapy, marking a new era in the treatment of this disease. Ayvakyt is the first approved medicine for both ISM and advanced SM, and our team is committed to bringing this transformative therapy to patients across the spectrum of disease,” he said. Ayvakit has already been approved by the EC to treat certain patients with aggressive systemic mastocytosis, SM with an associated haematological neoplasm, mast cell leukaemia and unresectable or metastatic gastrointestinal stromal tumours.