UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of Earliest Event
Reported):
(Exact name of registrant as specified in its charter)
|
(State or other jurisdiction of incorporation) |
(Commission File Number) | (I.R.S. Employer Identification No.) |
|
|
||
| (Address of principal executive offices) | (Zip Code) |
Registrant’s telephone
number, including area code: (
(Former name or former address, if changed since last report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) | ||
| Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) | ||
| Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) | ||
| Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth
company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.
Securities registered pursuant to Section 12(b) of the Exchange Act:
| Title of each class | Trading symbol(s) | Name of each exchange on which registered |
Item 8.01 Other Events.
On August 17, 2022, Blueprint Medicines Corporation issued a press release and hosted an investor call and live webcast to announce the top-line data from the registrational Part 2 of its PIONEER clinical trial of AYVAKIT® (avapritinib) in patients with non-advanced systemic mastocytosis (SM) demonstrating clinically meaningful and highly significant improvements across the primary and all key secondary endpoints. A copy of the press release and the presentation from the investor call are filed herewith as Exhibit 99.1 and Exhibit 99.2, respectively, to this Current Report on Form 8-K and incorporated herein by reference.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits.
| Exhibit No. | Description | |
| 99.1 | Press release issued by Blueprint Medicines Corporation on August 17, 2022 | |
| 99.2 | Presentation by Blueprint Medicines Corporation at investor call on August 17, 2022 | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document and incorporated as Exhibit 101) |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| BLUEPRINT MEDICINES CORPORATION | ||
| Date: August 17, 2022 | By: |
/s/ Kathryn Haviland |
| Kathryn Haviland | ||
| Chief Executive Officer | ||
Exhibit 99.1
Blueprint Medicines Announces Positive Top-line Results from PIONEER Trial of AYVAKIT® (avapritinib) in Patients with Non-Advanced Systemic Mastocytosis Achieving Primary and All Key Secondary Endpoints
-- AYVAKIT showed a superior mean change in total symptom score (p=0.003), compared to placebo plus best available care --
-- Highly significant reductions across all objective measures of mast cell burden reinforce the disease modifying activity of AYVAKIT --
-- AYVAKIT had a favorable safety profile compared to the control arm, supporting potential for long-term
treatment --
-- Plan to submit supplemental new drug application to FDA in fourth quarter of 2022 --
-- Blueprint Medicines to host investor conference call and webcast today at 8:00 a.m. ET --
CAMBRIDGE, Mass. – August 17, 2022 – Blueprint Medicines Corporation (NASDAQ: BPMC) today announced positive top-line results from the registrational Part 2 of the PIONEER clinical trial of AYVAKIT® (avapritinib) in patients with non-advanced systemic mastocytosis (SM) demonstrating clinically meaningful and highly significant improvements across the primary and all key secondary endpoints, including patient-reported symptoms and objective measures of mast cell burden. Based on these top-line data, Blueprint Medicines plans to submit a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration (FDA) for AYVAKIT in non-advanced SM in the fourth quarter of 2022, with a subsequent submission of a type II variation marketing authorization application to the European Medicines Agency (EMA) anticipated in 2023. In addition, Blueprint Medicines plans to present detailed data from the PIONEER trial at an upcoming medical meeting.
The trial, which was designed to assess AYVAKIT plus best available care versus placebo plus best available care (control arm), achieved its primary endpoint with a highly significant difference in the mean change in total symptom score (TSS) at 24 weeks (p=0.003). TSS was assessed by the Indolent SM Symptom Assessment Form (ISM-SAF). The AYVAKIT arm had a reduction of 15.6 points in mean TSS at 24 weeks, which continued to deepen to 20.2 points at 48 weeks in patients who rolled over to the Part 3 open-label extension study. At 24 weeks, the control arm had a reduction of 9.2 points in mean TSS. In addition, the PIONEER trial met all key secondary endpoints, including significant improvements across all measures of mast cell burden. More than half of AYVAKIT-treated patients had a ≥50 percent reduction of serum tryptase, compared to no patients in the control arm (53.9% vs. 0%; p<0.0001). AYVAKIT was well-tolerated and had a favorable safety profile, and 96.5 percent of AYVAKIT-treated patients completed 24 weeks of therapy, compared to 93.0 percent for the control arm. Overall, 0.7 percent of patients in the AYVAKIT arm and no patients in the control arm discontinued due to treatment-related adverse events.
“As a physician and clinical researcher who has been treating non-advanced systemic mastocytosis patients for over 25 years, I have been awaiting a therapy that decreases the abnormal mast cell burden and activation, improves a wide range of symptoms, and ultimately provides an improved quality of life to patients,” said Mariana Castells, M.D., Ph.D., Director, Mastocytosis Center, Brigham and Women’s Hospital, and an investigator on the PIONEER trial. “For patients with non-advanced SM, PIONEER is the first study to show significant clinical improvements over best available care across patient-reported symptoms and objective measures of disease, with a safety and tolerability profile supporting chronic treatment. The trial results suggest that if approved, AYVAKIT would represent a practice-changing treatment, enabling important clinical benefits for a broad range of patients with non-advanced SM.”
“The PIONEER results showcase Blueprint Medicines’ dedication to advancing the promise of precision therapy for patients with significant medical needs,” said Becker Hewes, M.D., Chief Medical Officer at Blueprint Medicines. “AYVAKIT has the potential to be the first approved medicine for non-advanced SM, and the only treatment that would address the genetic root cause across advanced and non-advanced forms of the disease. Today’s milestone represents a watershed moment for the systemic mastocytosis community and Blueprint Medicines, capping a decade of collaboration with clinicians, advocates and patients to transform standards of care, and to deepen the understanding of this disease and its impact on various aspects of patients’ lives.”
AYVAKIT was designed to potently and selectively inhibit D816V mutant KIT, the driver of SM in about 95 percent of cases. SM often leads to debilitating skin, gastrointestinal, neurocognitive and other systemic symptoms, such as life-threatening anaphylaxis.
“Non-advanced systemic mastocytosis is a lifelong disease with severe physical, emotional and social impacts that profoundly reduce patients’ quality of life,” said Lauren Denton, Executive Director of The Mast Cell Disease Society. “Patients with SM continue to be challenged by efforts to avoid various triggers of everyday life while also managing complex therapies. The PIONEER clinical trial results offer hope to these patients and help pave the way for new innovation in treatment.”
“These new data are the culmination of a dedicated long-term collaboration and shared ‘patients first’ core value between Blueprint Medicines and The Mast Cell Disease Society. We are excited by these results and further energized to work together with these exceptional investigators to transform the lives of patients, offering them a better quality of life and the gift of time,” said Valerie Slee, Board Chair of The Mast Cell Disease Society.
Top-line Data from the PIONEER Trial
Part 2 of the registrational PIONEER trial was designed to evaluate the efficacy and safety of AYVAKIT (25 mg once-daily dosing; N=141) versus control (N=71) over 24 weeks of treatment. Eligibility criteria include an indolent SM diagnosis confirmed by central pathology review, and moderate-to-severe symptom burden despite an optimized regimen of best available care. Patients were able to continue symptom-directed therapies while receiving AYVAKIT or placebo. Results were reported as of a data cutoff date of June 23, 2022.
Baseline data, including mean TSS, were consistent with Part 1 of the trial. The PIONEER study achieved its primary endpoint and all key secondary endpoints, with AYVAKIT showing highly significant improvements in patient-reported symptoms and objective measures of disease burden.
| Clinical Outcome Measures: AYVAKIT Arm vs. Control Arm | P-valuea | |
| Primary Endpoint | Mean Change in TSS | p=0.003 |
|
Secondary Endpointsb
|
≥30% Reduction in Mean TSS | p=0.009 |
| ≥50% Reduction in Mean TSS | p=0.005 | |
| Mean Change in Most Severe Symptom Score | p=0.015 | |
| ≥50% Reduction in Serum Tryptase | p<0.0001 | |
| ≥50% Reduction in KIT D816V Variant Allele Fraction | p<0.0001 | |
| ≥50% Reduction in Bone Marrow Mast Cell Aggregates | p<0.0001 | |
a One-sided p-value <0.025 indicates statistical significance.
b For secondary endpoints, reductions in TSS and objective measures of mast cell burden represent proportion of patients with ≥30% and ≥50% reductions. All endpoints are key secondary endpoints, except for mean change in most severe symptom score, which is an additional secondary endpoint.
AYVAKIT had a favorable safety profile compared to the control arm. The rate of adverse events (AEs) was 90.8 percent in the AYVAKIT arm and 93.0 percent in the control arm. Serious AEs occurred in 5.0 percent of AYVAKIT-treated patients, compared to 11.3 percent of patients in the control arm. Discontinuations due to treatment-related AEs occurred in 0.7 percent of AYVAKIT-treated patients and 0 percent of patients in the placebo arm. The AYVAKIT arm had a lower rate of cognitive AEs than the control arm (2.8% AYVAKIT vs. 4.2% control), and there were no intracranial bleeding events. Treatment-related AEs reported in at least three patients in either arm and at least 5 percent of AYVAKIT-treated patients included headache (7.8% AYVAKIT vs. 9.9% control), nausea (6.4% AYVAKIT vs 8.5% control), peripheral edema (6.4% AYVAKIT vs. 1.4% control) and periorbital edema (6.4% AYVAKIT vs. 2.8% control). In the AYVAKIT arm, 93.0 percent of edema AEs were Grade 1 and the remainder were Grade 2.
Conference Call Information
Blueprint Medicines will host a live conference call and webcast at 8:00 a.m. ET today to discuss the top-line data from the PIONEER trial. The conference call may be accessed by dialing 844-200-6205 (domestic) or 929-526-1599 (international), and referring to conference ID 806215. A webcast of the call will also be available under “Events and Presentations” in the Investors & Media section of the Blueprint Medicines website at http://ir.blueprintmedicines.com/. The archived webcast will be available on the Blueprint Medicines website approximately two hours after the conference call and will be available for 30 days following the call.
About AYVAKIT (avapritinib)
AYVAKIT (avapritinib) is a kinase inhibitor approved by the FDA for the treatment of 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 in Europe (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.
AYVAKIT/AYVAKYT is not approved for the treatment of any other indication in the U.S. or Europe. The FDA granted breakthrough therapy designation to AYVAKIT for the treatment of moderate to severe indolent SM.
To learn about ongoing or planned clinical trials, contact Blueprint Medicines at medinfo@blueprintmedicines.com or 1-888-BLU-PRNT (1-888-258-7768). Additional information is available at blueprintclinicaltrials.com or clinicaltrials.gov.
About Systemic Mastocytosis
Systemic mastocytosis (SM) is a rare disease primarily driven by the KIT D816V mutation. Uncontrolled proliferation and activation of mast cells result in chronic, severe and often unpredictable symptoms for patients across the spectrum of SM. The vast majority of those affected have non-advanced (indolent or smoldering) SM, with debilitating symptoms that lead to a profound, negative impact on quality of life. 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. Across advanced SM subtypes, the median overall survival is approximately 3.5 years in ASM, approximately two years in SM-AHN and less than six months in MCL.
Debilitating symptoms, including anaphylaxis, maculopapular rash, pruritis, diarrhea, brain fog, fatigue and bone pain, often persist across all forms of SM despite treatment with a number of symptom-directed therapies. 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 SM that selectively inhibit D816V mutant KIT.
About the PIONEER Trial
PIONEER is a randomized, double-blind, placebo-controlled, registrational trial evaluating AYVAKIT in patients with non-advanced SM. The trial includes three parts: dose-finding Part 1, registrational Part 2 and long-term treatment Part 3. Key trial endpoints include the change in patient-reported disease symptoms as measured by the ISM-SAF TSS, patient-reported quality of life, quantitative measures of mast cell burden and safety. Patients who completed Part 1 or 2 were eligible to participate in Part 3. All patients receive AYVAKIT treatment during Part 3, including those rolling over from the control arm. For more information about the PIONEER trial, please visit www.clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT03731260).
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 approved medicines directly to patients in the United States and Europe, and we are globally advancing multiple programs for systemic mastocytosis, lung cancer and other genomically defined cancers, and cancer immunotherapy. For more information, visit www.BlueprintMedicines.com 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 plans to submit a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration (FDA) for AYVAKIT in patients with non-advanced SM, with a subsequent submission of a type II variation marketing authorization application to the European Medicines Agency (EMA), plans and timing for presenting detailed data from the PIONEER trial of AYVAKIT in patients with non-advanced SM, and expectations regarding the potential benefits of AYVAKIT in treating patients with non-advanced SM. 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 the impact of the COVID-19 pandemic to Blueprint Medicines’ business, operations, strategy, goals and anticipated milestones, including Blueprint Medicines’ ongoing and planned research and discovery activities, ability to conduct ongoing and planned clinical trials, clinical supply of current or future drug candidates, commercial supply of current or future approved products, and launching, marketing and selling current or future approved products; Blueprint Medicines’ ability and plans in continuing to establish 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 or of an approved product in an additional indication 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 risk that “topline” data from our clinical trials that we announce or publish from time to time may change as more patient data become available and are subject to confirmation, audit, and verification procedures that could result in material changes in the final data; 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; Blueprint Medicines’ ability to develop and commercialize companion diagnostic tests for AYVAKIT/AYVAKYT; 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.
Investor Relations Contact
Jenna Cohen
+1 (857) 209-3147
ir@blueprintmedicines.com
Media Relations Contact
Andrew Law
+1 (617) 844-8205
media@blueprintmedicines.com
Exhibit 99.2
| © 2022 Blueprint Medicines Corporation R.S., living with systemic mastocytosis PIONEER Part 2 Top-line Results AYVAKIT® (avapritinib) in Non-Advanced Systemic Mastocytosis August 17, 2022 |
| Blueprint Medicines call participants 2 Introduction Kate Haviland, Chief Executive Officer Positive PIONEER Part 2 Topline Results Becker Hewes, MD, Chief Medical Officer Investigator Commentary Mariana Castells, MD, PhD, Director, Mastocytosis Center, Brigham and Women’s Hospital Q&A All PREPARED REMARKS Not for promotional use. |
| Forward-looking statements 3 This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding plans to submit a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration (FDA) for AYVAKIT in non-advanced SM, with a subsequent submission of a type II variation marketing authorization application to the European Medicines Agency (EMA), plans and timing for presenting detailed data from the PIONEER trial of AYVAKIT in patients with non-advanced SM, and, expectations regarding the potential benefits of AYVAKIT in treating patients with non-advanced SM. 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 presentation 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 presentation, including, without limitation, risks and uncertainties related to the impact of the COVID-19 pandemic to Blueprint Medicines’ business, operations, strategy, goals and anticipated milestones, including Blueprint Medicines’ ongoing and planned research and discovery activities, ability to conduct ongoing and planned clinical trials, clinical supply of current or future drug candidates, commercial supply of current or future approved products, and launching, marketing and selling current or future approved products; Blueprint Medicines’ ability and plans in continuing to establish 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 AYVAKIT/AYVAKYT; Blueprint Medicines’ ability to successfully demonstrate the safety and efficacy of its drug candidates and gain approval of its drug candidates or of an approved product in an additional indication 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 risk that “top-line" data from our clinical trials that we announce or publish from time to time may change as more patient data become available and are subject to confirmation, audit, and verification procedures that could result in material changes to the final data; 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 develop and commercialize companion diagnostic tests for AYVAKIT/AYVAKYT, 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 presentation 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. Blueprint Medicines, AYVAKIT, AYVAKYT and associated logos are trademarks of Blueprint Medicines Corporation. Not for promotional use. |
| AYVAKIT® (avapritinib) has the potential to be the first disease-modifying therapy for non-advanced SM SM, systemic mastocytosis 4 POSITIVE TOPLINE RESULTS FULL RESULTS EXPECTED AT UPCOMING MEDICAL CONFERENCE Not for promotional use. |
| Today’s news reflects a decade of commitment and collaboration SM, systemic mastocytosis; FDA, U.S. Food & Drug Administration; US, United States; EU, Europe 5 • Generated robust datasets on SM disease burden in collaboration with patients, healthcare providers, and patient advocacy groups • >100 scientific presentations and publications OUR VISION TO IMPROVE SM PATIENT OUTCOMES Advance the understanding of SM Pioneer scientific and clinical innovation Deliver transformative medicines to patients • Designed the first precision therapy to specifically target KIT D816V, the underlying cause of SM • Granted FDA breakthrough therapy designations for advanced and moderate-to-severe indolent SM • Conducted the first and only positive registrational study in non- advanced SM • AYVAKIT is approved for advanced SM in the U.S. and EU • ~1000 patients with SM have received AYVAKIT in the clinical or commercial settings • BLU-263 in development for mast cell disorders Not for promotional use. |
| AYVAKIT demonstrated highly significant and clinically meaningful impact on the primary and all key secondary endpoints Data cutoff as of June 23, 2022. 1. One-sided p-value < 0.025 indicates statistical significance. 2. For secondary endpoints, reductions in TSS and objective measures of mast cell burden represent proportion of patients with ≥30% and ≥50% reductions. All endpoints are key secondary endpoints, except for “Mean Change in Most Severe Symptom Score”, which is an additional secondary endpoint. TSS, total symptom score; VAF, variant allele fraction; MC, mast cell 6 Primary Endpoint Mean Change in TSS 0.003 Secondary Endpoints2 ≥30% Reduction in TSS 0.009 ≥50% Reduction in TSS 0.005 Mean Change in Most Severe Symptom Score 0.015 ≥50% Reduction in Serum Tryptase <0.0001 ≥50% Reduction in KIT D816V VAF <0.0001 ≥50% Reduction in Bone Marrow MC Aggregates <0.0001 Not for promotional use. P VA L U E 1 CLINICAL OUTCOME MEASURES |
| Positive PIONEER Part 2 Topline Results Becker Hewes, MD, Chief Medical Officer |
| Largest clinical trial in non-advanced SM conducted to-date Data cutoff as of June 23, 2022. QD, once daily; BAC, best available care; TSS, total symptom score; SD, standard deviation 8 Not for promotional use. Primary endpoint AYVAKIT 25 mg QD + BAC Placebo QD + BAC (Control) Mean change in TSS at 24 weeks AYVAKIT 25 mg QD + BAC Rollover (Part 3) Randomize 2:1 • Age ≥18 years • ISM confirmed by central pathology review • No restriction on prior therapy • Moderate-to-severe symptoms Eligibility • Similar between AYVAKIT and control arms • Consistent with PIONEER Part 1 • Median BAC across both arms was 3 (range 0 – 11) Baseline Characteristics AYVAKIT Control Enrolled 141 71 TSS score, mean (SD) 50.2 (19.1) 52.4 (19.8) |
| AYVAKIT demonstrated highly significant and clinically meaningful impact on the primary and all key secondary endpoints Data cutoff as of June 23, 2022. 1. One-sided p-value < 0.025 indicates statistical significance. 2. For secondary endpoints, reductions in TSS and objective measures of mast cell burden represent proportion of patients with ≥30% and ≥50% reductions. All endpoints are key secondary endpoints, except for “Mean Change in Most Severe Symptom Score”, which is an additional secondary endpoint. TSS, total symptom score; VAF, variant allele fraction; MC, mast cell 9 Primary Endpoint Mean Change in TSS 0.003 Secondary Endpoints2 ≥30% Reduction in TSS 0.009 ≥50% Reduction in TSS 0.005 Mean Change in Most Severe Symptom Score 0.015 ≥50% Reduction in Serum Tryptase <0.0001 ≥50% Reduction in KIT D816V VAF <0.0001 ≥50% Reduction in Bone Marrow MC Aggregates <0.0001 Not for promotional use. P VA L U E 1 CLINICAL OUTCOME MEASURES |
| Decreases in patient-reported symptoms and objective measures of disease burden 1. After 24 weeks, all patients had the option to cross over into Part 3 and receive treatment with AYVAKIT 25 mg QD. TSS, total symptom score; CI, confidence interval. 10 Mean Change in TSS [95 % CI] AYVAKIT Control PART 2: 24 weeks PART 3: 48 weeks1 PART 2: 24 weeks -15.6 [-18.6 –-12.6] -20.2 [-24.7 –-15.7] -9.2 [-13.1 –-5.2] Not for promotional use. ≥50% Reduction in Serum Tryptase [95% CI] AYVAKIT Control PART 2: 24 weeks PART 2: 24 weeks 53.9% [45.3 – 62.3] 0.0% [0.0 – 5.1] Rapid and further deepening in mean TSS reduction observed in Part 3 when control switched over to receive AYVAKIT |
| AYVAKIT was well-tolerated with a safety profile favorable to control Data cutoff as of June 23, 2022. 1. Cognitive effect AEs refer to 17 pooled terms identified across AYVAKIT clinical studies. AE, adverse event; SAE, serious adverse event; TRAE, treatment-related adverse event; ICB, intracranial bleed 11 AYVAKIT Control AEs, n (%) 128 (90.8) 66 (93.0) SAEs, n (%) 7 (5.0) 8 (11.3) Discontinuation due to TRAEs, n (%) 1 (0.7) 0 (0.0) TRAEs in ≥5% of AYVAKIT patients, by preferred term Headache, n (%) 11 (7.8) 7 (9.9) Nausea, n (%) 9 (6.4) 6 (8.5) Peripheral edema, n (%) 9 (6.4) 1 (1.4) Periorbital edema, n (%) 9 (6.4) 2 (2.8) • No ICB events • Lower rate of cognitive effect AEs1 reported for AYVAKIT (2.8%) vs. control (4.2%) • No Grade 3 cognitive effect AEs1 for AYVAKIT (0%) vs. control (1.4%) • In the AYVAKIT arm, 93.0% of edema AEs were Grade 1, with remainder Grade 2 • Higher Part 2 completion rate for AYVAKIT (96.5%) vs. control (93.0%) Not for promotional use. |
| Investigator Commentary Mariana Castells, MD, PhD, Director, Mastocytosis Center Brigham and Women’s Hospital |
| Dr. Mariana Castells, MD, PhD • Brigham and Women’s Hospital o Sees approximately 2,000 SM patients per year o Director, Mastocytosis Center; Drug Hypersensitivity and Desensitization Center; Allergy and Clinical Immunology Training Program • Professor, Harvard Medical School • Board of Directors: AAAAI, ABAI o AAAAI Foundation Research Chair • Clinical interests: drug allergy, anaphylaxis, mast cell activation disorders, urticaria, immune deficiencies, food and environmental allergies, and asthma SM, systemic mastocytosis; AAAAI, American Academy of Allergy, Asthma & Immunology; ABAI, American Board of Allergy and Immunology. 13 Not for promotional use. |
| Upon activation of mast cells, proinflammatory mediators are released 1. Castells M, Austen KF. Int Arch Allergy Immunol. 2002 Feb;127(2):147-52. 2. Castells M. J Allergy and Clin Immunol. 2017 Aug;140(2):321-333. Not for promotional use. 14 |
| Uncontrolled mast cell activation in SM causes severe and unpredictable symptoms across multiple organ systems1-3 1. Theoharides TC et al. N Engl J Med. 2015;373(2):163-172. 2. Gilreath JA et al. Clin Pharmacol. 2019;11:77-92. 3. Jennings SV et al. Immunol Allergy Clin North Am. 2018;38(3):505- 525. 4. Amin K. Respir Med. 2012;106(1):9-14. SM, systemic mastocytosis. 15 Mast cell Polypharmacy is characteristic • H1 and H2 antihistamines • Proton pump inhibitors • Leukotriene inhibitors • Anaphylaxis with hypotension and syncope • Dizziness • Palpitations Cardiovascular Gastrointestinal • Abdominal pain or cramping • Diarrhea • Heartburn or reflux • Nausea and/or vomiting • Bone pain • Muscle pain • Osteoporosis/osteopenia Musculoskeletal • Dyspnea • Nasal congestion • Throat swelling • Wheezing Respiratory • Darier’s sign • Dermatographism • Extreme flushing • Pruritus Skin • Anaphylaxis • Fatigue • Malaise • Weight loss Systemic Neuropsychiatric • Anxiety • Brain fog • Depression • Lack of focus/memory • Memory loss • Migraines • Corticosteroids • Cromolyn sodium • Anti-IgE antibody • Bisphosphonates • EpiPen Not for promotional use. |
| Case study #1 in a patient with significant skin and GI involvement 16 Spots Score 9 After almost two years on AYVAKIT, patient reports “life changing” improvement, including continued improvement in QoL, no new symptoms, and reduction in polypharmacy. This patient remains on AYVAKIT today. Severe ongoing symptoms; highly reduced QoL • Skin: lesions > 80%; triggered by sun, exercise, alcohol, stress, medical procedures • GI: recurrent, unpredictable heartburn, diarrhea, nausea First symptoms in 2009 ISM diagnosis in 2011 KIT D816V positive Ranitidine; famotidine; omalizumab; cetirizine; Benadryl, Epipen MEANINGFUL REDUCTIONS IN TSS AND SERUM TRYPTASE AT 24 WEEKS Data cutoff as of June 23, 2022. ISM, indolent systemic mastocytosis; GI, gastrointestinal; TSS, total symptom score; QoL, quality of life 75% reduction in serum tryptase 23-point TSS reduction Not for promotional use. |
| Case study #2 in a patient heavily pretreated with cytoreductive therapies and ongoing polypharmacy 17 Spots Score 9 Patient reports drastic symptom improvement including reduction in baseline skin lesions, rare GI symptoms, and consistent improvement in bone pain. This patient remains on AYVAKIT today. Severe and progressing symptoms • Skin: Chest/back lesions grew and spread 2000 – 2010; lesions flare with triggers; episodes of flushing, hiving, redness, swelling • GI: restricted diet to control pain, bloating, diarrhea, nausea, vomiting First symptoms in childhood KIT D816V positive Cromolyn, doxepin, cimetidine, hydroxyzine, Benadryl, EpiPen, prednisone; prior montelukast, omalizumab, hydroxyurea, interferon alpha MEANINGFUL REDUCTIONS IN TSS AND SERUM TRYPTASE AT 24 WEEKS 57% reduction in serum tryptase 7-point TSS reduction Not for promotional use. Data cutoff as of June 23, 2022. GI, gastrointestinal; TSS, total symptom score |
| PIONEER Part 2 positive topline results 18 Not for promotional use. AYVAKIT demonstrated highly significant and clinically meaningful impact on the primary and all key secondary endpoints 1 AYVAKIT was well-tolerated with a safety profile favorable to control 2 Detailed results expected to be presented at a future scientific congress 4 Plan to submit sNDA by end of the year 5 Decreases in patient-reported and objective measures of disease burden demonstrate clinically meaningful, disease-modifying benefit of AYVAKIT 3 Data cutoff as of June 23, 2022. sNDA, supplemental new drug application |
| Thank you Blueprint Medicines, AYVAKIT, GAVRETO and associated logos are trademarks of Blueprint Medicines Corporation. |
