Metastatic Gastrointestinal Stromal Tumor

Encouraging signs of activity were observed, including a 23% objective response rate (ORR) across all patients (median four prior lines of therapy) and a 43% ORR across second-line patients Favorable tolerability pro observed, consistent with use in front-line and second-line settings Data to be highlighted in an oral presentation today at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting PLYMOUTH, Mass.--(BUSINESS WIRE)-- IDRx, Inc., a clinical-stage biopharmaceutical company dedicated to transforming cancer treatment with purpose-built precision therapies, today announced updated preliminary clinical data from the Phase 1 portion of the company’s ongoing StrateGIST 1 study of IDRX-42 in patients with advanced gastrointestinal stromal tumors (GIST). These data will be highlighted today in an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. IDRX-42 is a novel, KIT mutant-selective, tyrosine kinase inhibitor (TKI) that has potent activity against both the key activating mutations and broad coverage of the clinically relevant resistance mutations in KIT-driven GIST. IDRX-42 was designed to overcome the twin challenges of on-target treatment resistance and off-target driven adverse events, which limit the clinical benefit of currently available TKIs. “There is a significant unmet medical need for next-generation therapies for GIST patients. Current standards of care either lack the breadth of resistance mutation coverage necessary for patients to realize long durations of response or disease stabilization, or they lack selectivity, resulting in unwanted side effects, or both,” said Professor Patrick Schöffski, M.D., M.P.H., Head of the Department of General Medical Oncology at the University Hospitals Leuven. “These promising Phase 1 data support the potential of IDRX-42 to provide meaningful clinical benefit for GIST patients, with encouraging evidence of clinical activity in patients with activating KIT mutations in exons 9 and 11, as well as in patients with clinically relevant resistance mutations in KIT, importantly those in exons 13 and 17.” Updated Preliminary Clinical Data Summary As of the data cut-off date of April 28, 2024, 73 patients have been treated with IDRX-42 in the Phase 1 portion of the ongoing StrateGIST 1 trial across dose cohorts ranging from 120 mg once daily (QD) to 600 mg twice daily (BID). All 73 patients had KIT-mutant GIST. 66 patients were evaluable for efficacy as of the time of the data cut-off. Patients who were efficacy evaluable must have had at least 1 post-baseline tumor assessment or had clinical progression or death before the first post-baseline tumor assessment. While a maximum tolerated dose was not reached, dose escalation in the Phase 1 portion of the trial has completed, and the Phase 1b dose confirmation portion of the trial has been initiated utilizing a dose of 300mg tablet formulation, which is equivalent to the 400mg capsule formulation. Patients were heavily pretreated, with a median of four prior lines of therapy. 19% (14/73) patients had received one prior line of therapy. 11% (8/73) patients had received two prior lines of therapy. 70% (51/73) patients had received three or more prior lines of therapy. 74% of patients remained on study treatment, and the median duration of treatment was 16 weeks as of the data cut-off. 100% of second line patients remained on treatment as of the data cut-off. The objective response rate (ORR) by modified RECIST v1.1 in the efficacy evaluable population was 23% (15/66) treated across all lines of therapy, of which all were partial responses (12 confirmed PRs, 3 pending confirmation). The ORR across second line patients was 43% (6/14; 4 confirmed PRs, 2 pending confirmation). In analyses of circulating tumor DNA (ctDNA), reductions in mutant allele fraction were observed consistently across KIT mutations detected in baseline samples. Reductions in mutant allele fraction, including to undetectable levels, as best response were observed in exon 9 and 11 activating mutations, and in resistance mutations exon 13, 14, and 17. IDRX-42 exhibited a favorable safety pro treatment-related adverse events (TRAEs) were mainly low grade. The most frequently reported TRAEs (≥20%) were gastrointestinal symptoms (diarrhea, nausea, decreased appetite, vomiting, dysgeusia) and fatigue. Gastrointestinal adverse events were Grade 1 in most patients, when they occurred. A low rate of dose modifications due to TRAEs was observed at the 400mg QD dose level, with only 6% dose reductions, 9% dose interruptions, and 0% discontinuations due to TRAEs. Dose-limiting toxicities (DLTs) were observed in 3/73 patients at doses of 600 mg, 800 mg and 1200 mg, respectively. All 3 patients elected to reduce dose and remained on study as of the data cut-off (range: >3 to >11 months); 2 of these patients have achieved a confirmed PR at a reduced dose of 400 mg QD. A flat and dose-linear pharmacokinetic pro observed. “In this dataset, IDRx has presented preliminary proof-of-concept of IDRX-42 supporting its potentially best-in-class pro patients with GIST,” said Tim Clackson, Ph.D., Chief Executive Officer of IDRx. “Importantly, we believe these efficacy and safety data support our plan to move IDRX-42 rapidly into early lines of therapy, including second-line and front-line, where patients haven’t seen a new treatment option in over 15 years.” “We are excited for these data to be presented today, as they support all aspects of our target product profile, including evidence of potent activity against relevant activating and resistance mutations in KIT, combined with a favorable safety profile,” said David Kerstein, M.D., Chief Medical Officer of IDRx. “Across a wide dose range and in this heavily pre-treated patient population, promising signs of clinical activity have been observed, and the initial data compares favorably against approved therapies and those in clinical development. We are encouraged by the emerging safety and tolerability profile, characterized mainly by low grade, manageable gastrointestinal adverse events with a notable lack of adverse events generally associated with off-target activity, such as hand-foot skin reaction and hypertension, supporting the overall selectivity of the molecule. We would like to express our gratitude to the patients and investigators for their participation in the ongoing StrateGIST 1 study.” The Data Will be Highlighted in an Oral Presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting: Title: StrateGIST 1: A first-in-human (FIH), phase 1 study of IDRX-42 in patients with metastatic gastrointestinal stromal tumors resistant to prior treatment with tyrosine kinase inhibitors (TKIs) Presenter: Patrick Schöffski, M.D., M.P.H. Abstract Number: 11501 Presentation Type: Oral Abstract Session Session Title: Sarcoma (Sub Track Gastrointestinal Stromal Tumors) Time: 3:12 P.M. CDT About GIST Gastrointestinal stromal tumors (GIST) are the most common subtype of soft tissue sarcoma. Approximately 80% of cases arise from gain of function mutations in the KIT receptor tyrosine kinase, driving the malignancy through constitutive activation of aberrant signaling. Resistance mutations in KIT emerge in ~90% of patients treated with imatinib, the current standard of care for GIST. In unresectable or metastatic GIST, clinical benefits from existing treatments can vary by mutation type. About the StrateGIST 1 Study StrateGIST 1 is an ongoing, open-label, first-in-human Phase 1/1b study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of IDRX-42 in patients with metastatic and/or surgically unresectable GIST after failure of imatinib and other approved drugs. The study is currently enrolling patients with documented pathogenic mutation in KIT or any platelet-derived growth factor receptor alpha (PDGFRA) mutation (other than PDGFRA exon 18) at sites in the U.S., Belgium, Germany and Spain. The Phase 1b portion will include expanded exploratory cohorts based on defined lines of prior TKI therapy. About IDRX-42 IDRX-42 is a potent, oral, highly selective KIT inhibitor targeting all major categories of activating and resistance mutations in patients with KIT-mutant GIST (including variants in exons 9, 11, 13 and 17). In preclinical studies, IDRX-42 demonstrated superior antitumor activity compared to imatinib, the current first-line of therapy, in GIST human xenograft models expressing mutations in KIT exons 9 and 11. In xenograft models expressing secondary resistance mutations in KIT exon 13 or 17, IDRX-42 treatment resulted in potent and dose-dependent antitumor activity superior to the second-line standard of care agent, sunitinib. IDRX-42 is currently being evaluated in a first-in-human Phase 1/1b study. About IDRx IDRx is a clinical-stage biopharmaceutical company dedicated to transforming cancer care with intelligently designed precision therapies. IDRx aims to address the limitations of today’s precision cancer medicines with highly potent and selective targeted therapies to stop key tumor escape mechanisms and prolong response to therapy. IDRx’s lead program is IDRX-42, designed to inhibit key genetic drivers and drug-resistant mutations of KIT in gastrointestinal stromal tumor (GIST). IDRx's pipeline also includes a second KIT inhibitor, IDRX-73. Founded in 2021, IDRx’s leadership team has extensive experience in drug development and collectively has been involved in the discovery, development, and commercialization of more than 10 approved medicines. To learn more, please visit and follow us on LinkedIn. View source version on businesswire.com: Contacts 1AB Katie Engleman katie@1abmedia.com Source: IDRx, Inc. View this news release online at:

-- Breadth of data across 7 presentations, including 4 oral, reflects continued leadership in advancing the understanding and treatment of systemic mastocytosis -- CAMBRIDGE, Mass., May 30, 2024 /PRNewswire/ -- Blueprint Medicines Corporation (Nasdaq: BPMC) today announced multiple upcoming datasets across two key conferences that reinforce the significant real-world burden of systemic mastocytosis (SM), and highlight the durable clinical outcomes of AYVAKIT®/AYVAKYT® (avapritinib) across the spectrum of the disease. The presentations, which build on over a decade of pioneering research with clinical experts and patient advocates, will be reported at the following meetings: European Academy of Allergy and Clinical Immunology (EAACI) Congress 2024, May 31 to June 3 European Hematology Association 2024 (EHA24) Hybrid Congress, June 13 to 16 "Our data reinforce the efficacy and safety of prolonged durations of AYVAKIT therapy, and highlight the urgency to diagnose and treat patients living with systemic mastocytosis," said Becker Hewes, M.D., Chief Medical Officer at Blueprint Medicines. "Based on unprecedented clinical datasets and the strength of our ongoing commercial launches in the U.S. and Europe, we have made significant progress toward establishing AYVAKIT as the global standard of care. We look forward to continued collaboration with the SM community to redefine what 'well-controlled' means for patients across the spectrum of the disease." PIONEER: With a median follow-up of more than two years, AYVAKIT showed durable efficacy and a favorable safety profile in patients with ISM. Safety data were consistent for the small number of patients (~10 percent) who dose escalated to 50 mg once daily. AYVAKIT led to sustained improvements in total symptom score and all symptom domains (assessed by the Indolent Systemic Mastocytosis Symptom Assessment Form), as well as quality of life (assessed by the Mastocytosis Quality of Life Score). AYVAKIT had a favorable safety and tolerability profile, with patients receiving up to four-plus years of treatment. The most common treatment-related adverse event (AE) was edema, with the majority reported as Grade 1, and the rate of treatment-related AEs leading to discontinuations remained low (3 percent). PATHFINDER: With a median follow-up of more than three years, the median overall survival (OS) for AYVAKIT has not been reached in patients with advanced SM. The median OS has not yet been reached regardless of disease subtype or prior therapy, reflecting the durable clinical benefits of AYVAKIT. In advanced SM, the historical median OS has ranged from less than six months to about 3.5 years.1 The overall response rate2 was 73 percent, and the rate of complete remission with full or partial hematologic recovery was 29 percent. AYVAKIT had a favorable benefit/risk profile consistent with previously reported data. Common treatment-related AEs were periorbital edema, thrombocytopenia, peripheral edema and anemia. PRISM: The largest European study to evaluate patient perspectives in SM reinforces the significant burden of disease, highlighting the urgency to treat. The Perceptions, Realities & Insights on SM (PRISM) Survey – a collaborative research project led by Blueprint Medicines and involving disease experts and patient organizations across seven countries – further illustrates the substantial impact of SM on patients' quality of life. Patients reported debilitating symptoms, impaired physical and mental health functioning, meaningful impacts on the ability to work, and significant polypharmacy use. Healthcare providers broadly recognized the burden of SM; 65 percent reported the disease affected patients' lives "quite a bit" or "a great deal," and 58 percent reported patients lost employment opportunities. At the start of their respective oral and poster sessions, data presentations will be made available in the "Science―Publications and Presentations" section of Blueprint Medicines' website. EAACI Congress 2024 Oral Presentation: Safety of Avapritinib in Indolent Systemic Mastocytosis (ISM): Longer Term Follow-up from the PIONEER Study (Abstract 000223) Oral Presentation: The Burden of Indolent Systemic Mastocytosis in Europe: Results from the PRISM Patient Survey (Abstract 000405) Oral Presentation: Identifying KIT D816V Mutation in Patients with Evidence of Systemic Mast Cell Activation (MCA) and Enriched for Hereditary Alpha-Typtasemia (HaT): Results from the PROSPECTOR Clinical Trial (Abstract 000403) Poster Presentation: Healthcare Provider Perspectives on Management of European Patients with Systemic Mastocytosis (Abstract 000413) EHA2024 Congress Oral Presentation: Avapritinib in Patients with Advanced Systemic Mastocytosis (AdvSM): Efficacy and Safety Analysis from the Phase 2 PATHFINDER Study with 3-Year Follow-up (Abstract S224) Poster Presentation: The Burden of Systemic Mastocytosis in Europe: Results from the PRISM Patient Survey (Abstract P1676) ePoster Presentation: Patient Diagnostic Journey of Systemic Mastocytosis in Europe: Results from the PRISM Survey (Abstract P2292) 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. Until 2023, there were 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 aggressive SM (ASM), SM with an associated hematological neoplasm (SM-AHN) and mast cell leukemia (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 ASM, SM-AHN and MCL, and adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. Under the brand name AYVAKYT (avapritinib), this medicine is approved by the European Commission for the treatment of adults with ISM with moderate to severe symptoms inadequately controlled on symptomatic treatment, adults with ASM, SM-AHN and MCL, after at least one systemic therapy, and adults with unresectable or metastatic GIST harboring the PDGFRA D842V mutation. The therapy is not recommended for the treatment of patients with low platelet counts (less than 50,000/µL). 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 the 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 global, fully integrated biopharmaceutical company that invents life-changing medicines. We seek to alleviate human suffering by solving important medical problems in two core focus areas: allergy/inflammation and oncology/hematology. Our approach begins by targeting the root causes of disease, using deep scientific knowledge in our core focus areas and drug discovery expertise across multiple therapeutic modalities. We have a track record of success with two approved medicines, including AYVAKIT®/AYVAKYT® (avapritinib) which we are bringing to patients with systemic mastocytosis (SM) in the U.S. and Europe. Leveraging our established research, development, and commercial capability and infrastructure, we now aim to significantly scale our impact by advancing a broad pipeline of programs ranging from early science to advanced clinical trials in mast cell diseases including SM and chronic urticaria, breast cancer and other solid tumors. 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' operations, including its expectations for our current or future approved drugs and drug candidates; the potential benefits of AYVAKIT/AYVAKYT or any of our current or future drug candidates in treating patients; the strength of the AYVAKIT/AYVAKYT launches in the U.S. and Europe; and Blueprint Medicines' ability to establish AYVAKIT/AYVAKYT as the global standard of care for the treatment of SM. The words "aim," "may," "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," "estimate," "predict," "project," "potential," "opportunity," "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: the delay of any current or planned clinical trials or the development of the company's current or future drug candidates; the company's 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 possibility that preclinical and clinical results for the company's 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 the possibility patient enrollment rates may be delayed or slower than anticipated; the actions of regulatory agencies and how this may affect the initiation, timing and progress of clinical trials; the company's 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 the company's 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 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 the company's 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, the company explicitly disclaims any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. Footnotes 1 Sperr WR, Kundi M, Alvarez-Twose I, et al. International prognostic scoring system for mastocytosis (IPSM): a retrospective cohort study. Lancet Haematol. 2019;6(12):e638-e649. 2 Treatment response was defined as complete remission with full or partial hematologic recovery, partial remission or clinical improvement. Trademarks Blueprint Medicines, AYVAKIT, AYVAKYT and associated logos are trademarks of Blueprint Medicines Corporation. SOURCE Blueprint Medicines Corporation

-- 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