UNITED STATES
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CURRENT REPORT
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Item 7.01 Regulation FD Disclosure.
On January 8, 2024, Blueprint Medicines Corporation (the “Company”) issued a press release providing a business update, including its 2024 outlook. A copy of the press release is attached as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated by reference herein.
Also on January 8, 2024, the Company updated its corporate presentation to reflect certain business and strategic updates. The Company intends to use this presentation in meetings with members of the investment community and others from time to time, including its presentation by management at the 42nd Annual J.P. Morgan Healthcare Conference on January 8, 2024 at 10:30 a.m. PT (1:30 pm ET). A copy of the presentation is attached as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated by reference herein. A live webcast of the presentation and will be available on the “Events and Presentations” section of the Company’s website at http://ir.blueprintmedicines.com.
The information in Item 7.01 of this Current Report on Form 8-K, including Exhibit 99.1 and 99.2 attached hereto, is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits.
| Exhibit No. |
Description | |
| 99.1 | Press release issued by Blueprint Medicines Corporation on January 8, 2024 | |
| 99.2 | Corporate slide presentation of Blueprint Medicines Corporation dated January 8, 2024 | |
| 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: January 8, 2024 | By: | /s/ Kathryn Haviland |
| Kathryn Haviland | ||
| Chief Executive Officer | ||
Exhibit 99.1
Blueprint Medicines Highlights 2024 Corporate
Strategy and Business Priorities
at 42nd Annual J.P. Morgan Healthcare Conference
-- AYVAKIT® (avapritinib) launch in indolent systemic mastocytosis to drive strong revenue growth in 2024, with ongoing U.S. launch and recent EU approval --
-- Expanding mast cell disease leadership with oral wild-type KIT inhibitor, BLU-808, advancing into clinical development; IND submission planned in Q2 2024 --
-- Maintaining durable cash position through focused investment and global commercial execution --
-- Kate Haviland, Chief Executive Officer, to present at J.P. Morgan conference today at 10:30 a.m. PT (1:30 p.m. ET) --
SAN FRANCISCO, Calif., Jan. 8, 2024 /PR Newswire/ -- Blueprint Medicines Corporation (Nasdaq: BPMC) today outlined its 2024 corporate strategy to deliver accelerated revenue growth, sustainable research and development, and a clear path to profitability.
Kate Haviland, Chief Executive Officer of Blueprint Medicines, said:
“As we enter 2024, AYVAKIT’s early launch success in indolent systemic mastocytosis has grown our conviction that AYVAKIT has the potential to be a multi-billion-dollar therapy that will drive long-term growth into the next decade. We know that the first few quarters of a launch are critical in defining the trajectory of a new medicine, and we have built a strong foundation for success with AYVAKIT as we continue to drive growth in the U.S. and expand our launch in Europe this year.
Throughout 2023, we also made significant progress across our research and development pipeline enabling us to focus investments on our most promising programs. A core component of our growth strategy is to build on our leadership position in SM by expanding to other allergic-inflammatory diseases where mast cells play a core role in the biology, and we have integrated infrastructure that we can efficiently scale. Across our portfolio, we are investing in our most compelling opportunities to deliver innovative, life-changing medicines to patients, while maintaining a strong and sustainable financial profile.”
Focused investment strategy in 2024 to drive long-term growth and maintain durable cash position
| 1. | Prioritized programs for investment |
Blueprint Medicines is building portfolio scale in therapeutic areas where there are significant medical needs in large patient populations and the company has a deep understanding of biological pathways, a potential to drive best-in-class efficacy and an ability to leverage expertise and infrastructure.
Mast cell diseases
| · | Extend the company’s leadership position in systemic mastocytosis with the ongoing launch of AYVAKIT in the U.S. and EU and continued development of the next-generation KIT D816V inhibitor elenestinib. |
| · | Expand into larger patient populations with allergic-inflammatory diseases with BLU-808, an oral wild-type KIT inhibitor, including chronic urticaria and other diseases where mast cells are core to the biology. |
Breast cancer and other solid tumors
| · | Advance combination development of BLU-222, a highly selective CDK2 inhibitor with best-in-class potential, in HR+/HER2- breast cancer based on positive previously reported monotherapy clinical data. |
| · | Progress ongoing strategic partnership discussions to maximize the potential of BLU-222 as a backbone combination therapy in HR+/HER2- breast cancer and other CDK2-vulnerable cancers. |
| · | Advance additional programs including BLU-956, a next-generation CDK2 inhibitor development candidate nominated in 2023, and targeted protein degrader research programs for CDK2 and an undisclosed target to support long-term lifecycle management. |
| 2. | De-prioritized programs |
Blueprint Medicines is discontinuing investment in specific programs, based on the evolving external landscape, emerging clinical data and partnering considerations.
Lung cancer
| · | Discontinue further investment in the early clinical-stage therapies BLU-945 and BLU-451 for EGFR-mutant NSCLC and explore strategic options, including potential out-licensing, based on the evolving external landscape and emerging clinical data. |
| · | In February 2023, Blueprint Medicines announced Roche’s decision to terminate the global collaboration agreement for GAVRETO® (pralsetinib). Given Blueprint Medicines’ lack of global infrastructure in lung and thyroid cancer, the company has decided to discontinue global development and marketing of GAVRETO in territories excluding the U.S. and Greater China. The companies will continue working on transition and wind-down activities anticipated to begin in the first quarter of 2024; further information on product discontinuation timing to be provided in the near future. |
| · | Blueprint Medicines has identified a potential alternate partner for GAVRETO in the U.S. and is continuing to work with the involved parties to define a scenario that enables continued availability of GAVRETO in the U.S. |
| · | Blueprint Medicines expects the wind-down of the Roche collaboration for GAVRETO will result in significantly lower year-over-year operating expenses related to GAVRETO in 2024 and will not affect the $175 million upfront payment received under a 2022 financing agreement with Royalty Pharma. |
As a result of continued strategic portfolio prioritization, Blueprint Medicines expects a year-over-year decline in operating expenses in 2024. The company plans to provide financial guidance for 2024, including anticipated AYVAKIT revenue, when it reports fourth quarter and full-year 2023 financial results in February 2024.
2024 Corporate Milestones
The company's anticipated 2024 corporate milestones include:
Mast cell diseases
| · | Present long-term safety and efficacy data from the PIONEER trial of AYVAKIT in indolent SM (ISM) in the first half of 2024. |
| · | Submit an investigational new drug (IND) application for BLU-808 in the second quarter of 2024. |
| · | Initiate the registration-enabling Part 2 of the HARBOR trial of elenestinib in ISM in the second half 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. |
| · | Provide update on BLU-222 registration plan in HR+/HER2- breast cancer in the second half of 2024. |
J.P. Morgan Healthcare Conference Presentation Information
Kate Haviland, Chief Executive Officer of Blueprint Medicines, will present a company overview and 2024 outlook at the 42nd Annual J.P. Morgan Healthcare Conference on Monday, January 8 at 10:30 a.m. PT / 1:30 p.m. ET. A live webcast of the presentation and Q&A breakout session will be available by visiting the "Events and Presentations" section of Blueprint Medicines' website at http://ir.blueprintmedicines.com. A replay of the webcast will be archived on Blueprint Medicines' website for 30 days following the presentation.
About Blueprint Medicines
Blueprint Medicines is a global precision therapy company that invents life-changing medicines. Applying an approach that is both precise and agile, we create therapies that selectively target the root cause of disease, 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 have brought our approved medicines to patients in the United States and Europe, and we are globally advancing multiple programs for mast cell disorders, including systemic mastocytosis and chronic urticaria, breast cancer and other solid tumors. For more information, visit www.BlueprintMedicines.com 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 Blueprint Medicines' views with respect to AYVAKIT’s potential to be a multi-billion-dollar therapy; the continued growth of AYVAKIT in the U.S. and the expansion of AYVAKYT’s launch in Europe; the expansion of Blueprint Medicines’ mast cell disease franchise with the development of BLU-808; the advancement of its clinical development of BLU-222, preclinical development of BLU-956 and progression of targeted protein degrader research programs for CDK2; plans, strategies, timelines 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' financial performance, strategy, goals and anticipated milestones, business plans, outlook 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: preliminary activity and safety data may not be representative of more mature data; 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; the success of Blueprint Medicines' current and future collaborations, financing arrangements, partnerships or licensing arrangements may impact Blueprint Medicines' ability to capitalize on the market potential of its approved drugs and drug candidates; and 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. 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, GAVRETO and associated logos are trademarks of Blueprint Medicines Corporation.
Investor Relations Contact
Jenna Cohen
857-209-3147
ir@blueprintmedicines.com
Media Relations Contact
Andrew Law
617-844-8205
media@blueprintmedicines.com
Exhibit 99.2
Making Our Mission a Reality KATE HAVILAND, CHIEF EXECUTIVE OFFICER J.P. MORGAN HEALTHCARE CONFERENCE JANUARY 8, 2024 Adrianne Clinton patient living with systemic mastocytosis
Forward - Looking Statements 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, strategies, timelines and expectations for the company’s future business growth, including its 2024 growth strategy ; AYVAKIT’s potential to capture a blockbuster market opportunity in SM ; whether BLU - 808 has first - and best - in - class, pipeline in a pill potential ; whether any of the company’s product candidates will address unmet medical needs ; reduction of the company’s 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 company’s current or future approved drugs or drug candidates in treating patients ; and the company’s 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 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, the company’s ability and plans in continuing to expand a commercial infrastructure, and successfully launching, marketing and selling current or future approved products ; the company’s 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 the company’s current or future drug candidates ; the company’s advancement of multiple early - stage efforts ; 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 preclinical and clinical results for the company’s 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 ; the company’s ability to obtain, maintain and enforce patent and other intellectual property protection for AYVAKIT/AYVAKYT or any drug candidates it is developing ; the company’s ability to develop and commercialize companion diagnostic tests for AYVAKIT/AYVAKYT or any of its current and future drug candidates ; the company’s ability to successfully expand its operations, research platform and portfolio of therapeutic candidates, and the timing and costs thereof ; and the success of the company’s current and future collaborations, financing arrangements, partnerships or licensing arrangements ; and risks and uncertainties related to the impact of the COVID - 19 pandemic to the company’s business, operations, strategy, goals and anticipated milestones, including the company’s 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 . These and other risks and uncertainties are described in greater detail in the section entitled “Risk Factors” in the company’s filings with the Securities and Exchange Commission (SEC), including the company’s 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 the company has made or may make with the SEC in the future . The forward - looking statements in this presentation are made only as of the date hereof, and except as required by law, the company undertakes no obligation to update any forward - looking statements contained in this presentation as a result of new information, future events or otherwise . Accordingly, readers are cautioned not to place undue reliance on these forward - looking statements . This presentation also contains estimates, projections and other statistical data made by independent parties and by the company relating to market size and growth and other data about the company's industry . These data involve a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates . In addition, projections, assumptions and estimates of the company's future performance and the future performance of the markets in which the company operates are necessarily subject to a high degree of uncertainty and risk . Blueprint Medicines, AYVAKIT, AYVAKYT and associated logos are trademarks of Blueprint Medicines Corporation . 2
The accelerating growth profile of Blueprint Medicines 3 Establishing leadership in SM Accelerating growth Incubating innovation Broad portfolio built organically through proprietary research platform Approval & launch of AYVAKIT ® ( avapritinib ) for AdvSM and ISM in the U.S. and EU Blockbuster opportunity in SM, focused investment in compelling growth opportunities , and a path to profitability 2011 – 2021 2021 – 2023 2024 – FUTURE Avapritinib is approved under the trade name AYVAKYT ® in Europe. AdvSM , advanced systemic mastocytosis ; ISM, indolent systemic mastocytosis ; SM, systemic mastocytosis A fully - integrated, commercial - stage, global biopharmaceutical company, with an accelerating growth profile <15 years from founding
Delivering business growth in 2024 and beyond 4 2023 Accomplishments 2024 Growth Strategy Launched AYVAKIT in ISM Delivered four Phase 1 clinical datasets informing future investment Nominated 3 DCs, including oral wild - type KIT inhibitor BLU - 808 Continued decline in operating expenses Significant revenue growth with AYVAKIT launch in SM Focused investment in compelling growth opportunities with potential to be significant value drivers Durable capital position allows for independence from capital markets DC, development candidate
Three key growth drivers in 2024 5 ALLERGY/ IMMUNOLOGY ONCOLOGY/ HEMATOLOGY Investing in Sustainable Innovation Maintaining Financial Strength Strong and steady global launch delivering growth well into the next decade Capturing a Blockbuster Opportunity
AYVAKIT has a unique and multidimensional value proposition 6 Blockbuster market opportunity Compelling clinical profile Multiple opportunities for growth Positive receptivity driving demand
AYVAKIT is capturing a blockbuster opportunity in SM 7 $28.6 $30.1 $39.1 $39.9 $54.2 Q3 2022 Q4 2022 Q1 2023 Q2 2023 Q3 2023 AYVAKIT NET PRODUCT REVENUE ($M) +36% May 22, 2023: FDA approval for ISM Significantly larger population with potential for chronic duration of treatment in ISM High - margin specialty drug with tractable call points First and only approved therapy to treat the underlying driver of disease Durable growth expected into next decade with long IP protection IP, intellectual property
AYVAKIT provides durable symptom control with a well - tolerated, once - daily pill 8 Broad and Durable Efficacy Improvement across broad range of skin, gastrointestinal, neurocognitive, and other symptoms Safety Profile Supporting Chronic Treatment Treatment durations up to 4+ years in PIONEER 1 ; long - term safety data to be presented in 2024 Range of Doses Multiple dose strengths meet the medical needs across a spectrum of SM patients 1. Blueprint Medicines data on file. As of November 2023, the median duration of therapy in PIONEER (n=251) was 25.1 months ( ran ge: 0.2 - 52.9 months). 8
Strong foun datio n and breadth of execution fuel near - term growth trajectory 9 1. Blueprint Medicines data on file. Percentages are based upon new SM patient starts in Q3 2023 visible in the SP/HUB channe l, which reflects the majority of AYVAKIT volume. Broad demand across provider types and channels Volume driven by new vs. existing prescribers ~60/40% Volume driven by academic vs. community accounts ~50/50% Commercial and medical execution driving awareness Growth in patient unaided AYVAKIT awareness vs. prior to launch 3.5X Patients likely to ask their doctor about AYVAKIT ~65% SM publications 70+ Educational speaker programs 230+ Regional SM conferences 300+ Ease of access Conversion rate from prescription to shipment ~95% Days time to fill for majority of patients < 10 Percent of lives with broad coverage to label >95%
Significant headroom for upside opportunity with growing SM market 10 • Broaden healthcare provider perspective on the AYVAKIT - eligible patient to align to our broad label • Build market through more efficient diagnosis • Enter new markets outside of the U.S. ~9,500 Diagnosed and uncontrolled ISM in U.S. 1 ~32,000 U.S. SM prevalence 2 >20% YoY growth ~21,000 Total SM diagnosed in U.S. 1 1. Blueprint Medicines data on file, based upon visibility of unique patients in US claims data. 2. Cohen et al 2014.
Capturing a Blockbuster Opportunity Three key growth drivers in 2024 11 ALLERGY/ IMMUNOLOGY ONCOLOGY/ HEMATOLOGY Investing in Sustainable Innovation Maintaining Financial Strength Focused investment to drive long - term growth
BLU - 222 CDK2 Ongoing partnering discussions BLU - 956 (next gen) CDK2 Targeted protein degrader CDK2 Global Targeted protein degrader Undisclosed AYVAKIT ® ( avapritinib ) 1 KIT D816V Global excluding Greater China 4 Elenestinib (next gen) KIT D816V Global BLU - 808 Wild - type KIT Additional undisclosed mast cell targets/modalities Building scale in two focused and exciting areas of science 12 Indolent SM 2 Advanced SM 3 Indolent SM Chronic urticaria HR+ / HER2 - breast cancer Other CDK2 vulnerable cancers HR+ / HER2 - breast cancer PROGRAM TARGET DISCOVERY CLINICAL COMMERCIAL RIGHTS HR+ / HER2 - breast cancer MAST CELL DISORDERS Allergy/inflammation focus: SOLID TUMORS Oncology focus: 1. Also approved in the U.S. for adults with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, including P DGF RA D842V mutations. Approved in Europe (AYVAKYT ® ) for adults with unresectable or metastatic GIST harboring the PDGFRA D842V mutation. 2. Approved in the U.S. for adults with indolent SM. Approved in Europe (AYVAKYT) for adults with indolent SM with mod erate to severe symptoms inadequately controlled on symptomatic treatment. 3. Approved in the U.S. for adults with advanced S M, including aggressive SM (ASM), SM with an associated hematological neoplasm (SM - AHN) and mast cell leukemia (MCL). Approved in Europe (AYV AKYT®) for adults with ASM, SM - AHN or MCL, after at least one systemic therapy. 4. CStone Pharmaceuticals has exclusive rights to develop and commercialize avapritinib in Greater China. Updated as of January 8, 2024. Additional programs Undisclosed Global
Mast cells are core drivers of biology in a range of inflammatory diseases 13 • KIT - mediated signaling plays a central role in survival, proliferation, and activation of mast cells • When degranulation occurs, release of inflammatory molecules leads to a broad range of physiological effects KIT is a clinically validated mast cell target prostaglandins KIT histamine cytokines tryptase degranulation MCAS, mast cell activation syndrom; GI, gastrointestinal
Elenestinib , an investigational next - generation, potent, selective KIT D816V inhibitor 14 – 22.2 – 28.5 – 31.8 – 33.6 – 40.0 – 35.0 – 30.0 – 25.0 – 20.0 – 15.0 – 10.0 – 5.0 0.0 Placebo (n=10) Elenestinib 25 mg QD (n=10) Elenestinib 50 mg QD (n=10) Elenestinib 100 mg QD (n=8) Mean % change from baseline Elenestinib Reductions in ISM - SAF Total Symptom Score 1. Tashi T. Et al. Presented at ASH 2023. Well - tolerated with no treatment discontinuations due to AEs; most AEs Grade 1/2 Improved disease - related symptoms as assessed by the validated ISM - SAF Reduced multiple biomarkers of mast cell burden Robust clinical activity and favorable tolerability observed across doses HARBOR PART 1 TRIAL RESULTS PRESENTED AT ASH 2023 1 :
Wild - type KIT inhibitor BLU - 808 has first - and best - in - class, pipeline in a pill potential 15 Vehicle IND submission planned for 2Q 2024 Attribute Ideal Candidate BLU - 808 pKIT / proliferation IC 50 < 10 nM pKIT IC 50 0.37/1.3 nM PDGFR / FLT3 selectivity > 50x / > 50x >300/>9600 Kinase Selectivity; S(10) < 0.1 0.042 Drug/Drug Interactions Low potential Low potential Peripherally Restricted Kpuu < 0.1 Kpuu 0.021 10 nM BLU - 808 • Preclinical treatment with BLU - 808 inhibits degranulation , targeting an underlying cause of inflammatory disease . • Images are frame capture from videos available at the QR code. PDGFR, platelet - derived growth factor receptor; FLT3, fms - like tyrosine kinase 3; Kpuu, unbound partition coefficient; IgE, immu noglobulin E; IND, investigational new drug
Targeting KIT with an oral therapy to address significant unmet medical needs 16 Typical presentation of hives or wheals, a common symptom in chronic urticaria 1 Disease Biology Driven by Mast Cells Target Validation wtKIT inhibition has established clinical proof - of - concept in chronic urticaria Approach Small molecule TKI; opportunity to drive market expansion with an oral regimen Significant disease burden and QoL impact due to itching, hives, swelling and related anxiety, sleep loss ~680K patients in US & EU4 1 Unmet need for an oral therapy that targets core biology Opportunity TKI, tyrosine kinase inhibitor; QoL, quality of life; EU4 includes France, Germany, Italy, Spain 1. Antihistamine refractory, claims - identified patients with CU in the US and EU4
BLU - 222 CDK2 Ongoing partnering discussions BLU - 956 (next gen) CDK2 Targeted protein degrader CDK2 Global Targeted protein degrader Undisclosed AYVAKIT ® ( avapritinib ) 1 KIT D816V Global excluding Greater China 4 Elenestinib (next gen) KIT D816V Global BLU - 808 Wild - type KIT Additional undisclosed mast cell targets/modalities Building scale in two focused and exciting areas of science 17 Indolent SM 2 Advanced SM 3 Indolent SM Chronic urticaria HR+ / HER2 - breast cancer Other CDK2 vulnerable cancers HR+ / HER2 - breast cancer PROGRAM TARGET DISCOVERY CLINICAL COMMERCIAL RIGHTS HR+ / HER2 - breast cancer MAST CELL DISORDERS Allergy/inflammation focus: SOLID TUMORS Oncology focus: 1. Also approved in the U.S. for adults with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, including P DGF RA D842V mutations. Approved in Europe (AYVAKYT ® ) for adults with unresectable or metastatic GIST harboring the PDGFRA D842V mutation. 2. Approved in the U.S. for adults with indolent SM. Approved in Europe (AYVAKYT) for adults with indolent SM with mod erate to severe symptoms inadequately controlled on symptomatic treatment. 3. Approved in the U.S. for adults with advanced S M, including aggressive SM (ASM), SM with an associated hematological neoplasm (SM - AHN) and mast cell leukemia (MCL). Approved in Europe (AYV AKYT®) for adults with ASM, SM - AHN or MCL, after at least one systemic therapy. 4. CStone Pharmaceuticals has exclusive rights to develop and commercialize avapritinib in Greater China. Updated as of January 8, 2024. Additional programs Undisclosed Global
With BLU - 222, we have solved the selectivity challenge of CDK2 inhibition 18 CDK2 is a clinically validated cell cycle target Large market with significant unmet need Comprehensive program to drive value $10B+ Global sales of CDK4/6 inhibitors for HR+/HER2 - breast cancer in 2023 Prevent and address CDK4/6 resistance as backbone of combination therapy Highly selective approach minimizing off - target toxicity to enable combination partner of choice Next - generation assets to maximize long - term value CDK, cyclin - dependent kinase; HR+, hormone receptor positive; HER2 - , human epidermal growth factor receptor 2 negative; SOC, sta ndard of care Selective CDK2 inhibition has historically been challenging to achieve
BLU - 222 has the potential to be the first and best - in - class selective inhibitor of CDK2 19 BLU - 222 1 PF - 4091 2 PRECLINICAL PROFILE Selectivity score / SI(10) 0.045 0.127 CDK2 potency / CDK2 enzyme IC 50 ( nM ) 2.6 7.2 PHASE 1 MONOTHERAPY DOSE ESCALATION DATA Patients 27 patients 35 patients Dose range tested 50 mg – 800 mg BID (MTD not determined) 75 mg – 500 mg BID (MTD: 300 mg BID) PK (average effective half life) ~12 hrs ~2 - 3 hrs Treatment emergent adverse events (TEAEs) No Gr5; 1 Gr4 (hypokalemia; unrelated) 1 Gr5 (unrelated); 1 Gr4 (neutropenia) HEMATOLOGIC TEAE s ALL GR3 GR4 ALL GR3 GR4 • Anemia 29.6% 3.7% 45.7% 8.6% • Neutropenia 3.7% 28.6% 14.3% 2.9% • Thrombocytopenia 3.7% 3.7% 20.0% 2.9% 1. Patel, M.R. et al, ASCO 2023 and Blueprint data on file. Data cut April 25, 2023. 2. Yap, T.A. et al, ASCO 2023
Capturing a Blockbuster Opportunity f Three key growth drivers in 2024 20 ALLERGY/ IMMUNOLOGY ONCOLOGY/ HEMATOLOGY Investing in Sustainable Innovation Maintaining Financial Strength Durable capital position with a clear path to profitability
$21 $53 $111 2020 2021 2022 2023 2024 2025 2026 2027+ AYVAKIT is capturing a blockbuster opportunity in SM Actual Will provide FY 2023 financials and 2024 AYVAKIT product revenue guidance at Q4/FY 2023 earnings call. ESTIMATED >$1.5B GLOBAL SM PEAK REVENUE 21 AYVAKIT Annual Net Product Revenue ($M) Figure is provided as a graphical representation and is not intended as financial guidance.
Portfolio prioritization driving continued operating expense reduction 22 Continued reduction in opex • Deprioritized investment decisions (e.g., EGFR) support anticipated opex reduction • Plan for continued opex reduction while still investing sustainably, allocating capital toward highest priority programs AYVAKIT revenue growth and opex reductions will drive continued decline in cash burn Operating Cash Burn will Continue to Decline in 2024+ Operating cash burn for 2023 is based upon unaudited results, to be announced at Q4/FY 2023 financial and operating results c all in February 2024. Figure is provided as a graphical representation and is not intended as financial guidance. 2022 2023 2024 Planned Expect YoY decline in opex and cash burn. Will provide 2024 commentary at Q4/FY 2023 earnings call
Key anticipated portfolio milestones in 2024 23 Area Program Milestone Timing Mast cell disorders AYVAKIT Present long - term safety and efficacy data from PIONEER trial in ISM 1H 2024 BLU - 808 IND submission 2Q 2024 Elenestinib Initiate registration - enabling Part 2 of the HARBOR trial in ISM 2H 2024 Solid tumors BLU - 222 Present data in combination with ribociclib and fulvestrant for HR+/HER2 - breast cancer 1H 2024 Provide update on registration plan for HR+/HER2 - breast cancer 2H 2024 In addition to AYVAKIT revenue growth , Blueprint expects the following data - related milestones in 2024:
Blueprint positioned to accelerate our business growth in 2024 and beyond 24 AYVAKIT is capturing a blockbuster opportunity in SM. AYVAKIT in SM is one of the most exciting rare disease launches happening today. Focused investment in growth opportunities that leverage our expertise. Pursuing exciting areas of science at the nexus of our deep understanding of core biology and our business strategy to drive growth through leverage and scale. On the path to profitability. With ramping revenues and a focused spending plan we are maintaining a durable capital position while also investing in opportunities for longer term growth.
BLU - 222 CDK2 Ongoing partnering discussions BLU - 956 (next gen) CDK2 Targeted protein degrader CDK2 Global Targeted protein degrader Undisclosed AYVAKIT ® (avapritinib) 1 KIT D816V Global excluding Greater China 4 Elenestinib (next gen) KIT D816V Global BLU - 808 Wild - type KIT Additional undisclosed mast cell targets/modalities Blueprint Medicines pipeline 25 Indolent SM 2 Advanced SM 3 Indolent SM Chronic urticaria HR+ / HER2 - breast cancer Other CDK2 vulnerable cancers HR+ / HER2 - breast cancer PROGRAM TARGET DISCOVERY CLINICAL COMMERCIAL RIGHTS HR+ / HER2 - breast cancer MAST CELL DISORDERS Allergy/inflammation focus: SOLID TUMORS Oncology focus: 1. Also approved in the U.S. for adults with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, including P DGF RA D842V mutations. Approved in Europe (AYVAKYT ® ) for adults with unresectable or metastatic GIST harboring the PDGFRA D842V mutation. 2. Approved in the U.S. for adults with indolent SM. Approved in Europe (AYVAKYT) for adults with indolent SM with mod erate to severe symptoms inadequately controlled on symptomatic treatment. 3. Approved in the U.S. for adults with advanced S M, including aggressive SM (ASM), SM with an associated hematological neoplasm (SM - AHN) and mast cell leukemia (MCL). Approved in Europe (AYV AKYT®) for adults with ASM, SM - AHN or MCL, after at least one systemic therapy. 4. CStone Pharmaceuticals has exclusive rights to develop and commercialize avapritinib in Greater China. Updated as of January 8, 2024. Additional programs Undisclosed Global