AHN, or MCL, after at least one systemic therapy. In December 2023, the European Commission approved AYVAKYT for the treatment of adult patients with indolent SM with moderate to severe symptoms inadequately controlled on symptomatic treatment. These approvals in advanced SM were supported by our ongoing Phase 1 clinical trial in advanced SM, which we refer to as our EXPLORER trial, and our ongoing Phase 2 clinical trial in advanced SM, which we refer to as our PATHFINDER trial. The FDA's approval of AYVAKI ...

Financial Data and Key Metrics Changes - The company reported total revenues of $96.1 million for Q1 2024, including $92.5 million from AYVAKIT net product revenue, which represents a year-over-year growth of over 135% [34][44][92] - AYVAKIT revenue guidance for the year has been increased to $390 million to $410 million, reflecting a strong revenue trajectory towards peak sales of over $2 billion globally [32][67][93] - The company maintains a strong financial position with $735.6 million in cash on hand and aims to reduce cash burn in 2024 [46][54] Business Line Data and Key Metrics Changes - AYVAKIT's net product revenue for Q1 2024 was $92.5 million, with $83.1 million from the US and $9.4 million from ex-US sales [34][44] - The company is seeing strong and steady growth in patients on AYVAKIT, with a strong pace of new patient starts and low discontinuation rates [34][92] - The mix of commercial versus free goods has skewed favorably, with commercial patients now comprising the majority of those on therapy [56][67] Market Data and Key Metrics Changes - The company is expanding its prescriber base across various specialties, with a notable increase in allergists prescribing AYVAKIT [113] - The international launch of AYVAKIT is off to a robust start, particularly in Germany, contributing to the overall revenue growth [56][108] - The unaided awareness of AYVAKIT among patients has grown nearly eightfold since approval, indicating significant market penetration potential [61][125] Company Strategy and Development Direction - The company is focused on expanding its pipeline in mast cell disorders, with BLU-808 being a key program aimed at addressing various indications beyond chronic urticaria [33][90] - The strategic partnership discussions are ongoing, particularly for the CDK2 program, which is expected to advance in the second half of the year [134] - The company aims to redefine disease control for providers and patients, enhancing awareness and education initiatives to drive growth [37][39] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in sustaining growth due to strong patient engagement and educational initiatives [39][92] - The company anticipates continued growth in net patient adds, driven by a strong cadence of new patient starts and favorable compliance rates [72][92] - Management highlighted the importance of building a sustainable business model while focusing on long-term value creation [119] Other Important Information - The company is preparing to file the IND for BLU-808 to initiate a Phase 1 study in healthy volunteers [33][122] - The company is also advancing its oncology portfolio, with plans to present data on BLU-222 at the upcoming ASCO meeting [43][112] Q&A Session Summary Question: What is the split between allergists and hematologists prescribing AYVAKIT? - Management noted a strong foundation in prescribing across both hematology and allergy immunology, with a balanced mix of prescribers [12][13] Question: What are the assumptions behind the updated guidance? - Management clarified that the guidance reflects strong growth expectations, with no anticipated slowdown in net patient adds [16][72] Question: How is the company addressing the potential patient population not currently being prescribed AYVAKIT? - The company is focused on identifying patients who are not well-controlled and increasing awareness through direct-to-consumer efforts [14][37] Question: What is the strategy for expanding into new indications for BLU-808? - The company plans to establish proof of concept in chronic urticaria before exploring additional indications based on the drug's profile [24][122] Question: How is the company measuring the success of its direct-to-consumer campaign? - Management highlighted the importance of patient storytelling and educational initiatives to enhance awareness and engagement [150][151]

First Quarter 2024 Financial Results Agenda AYVAKIT PERFORMANCE | --- | --- | --- | --- | --- | |-------|-------|-------------------------|-------|-------| | | | | | | | | | | | | | | | | | | | | | Q1 2024 FINANCIAL | | | | | | PERFORMANCE | | | | | | | | | | | | | | | | | | Mike Landsittel | | | | | | Chief Financial Officer | | | 2 3 INTRODUCTION Kate Haviland Chief Executive Officer THE POWERFUL MAST CELL Not for promotional use Forward-looking statements This presentation contains forward-looking statem ...

Blueprint Medicines Reports Strong First Quarter 2024 Results and Raises AYVAKIT®/AYVAKYT® (avapritinib) Full Year Revenue Guidance -- Raising guidance to $390 million to $410 million in full year AYVAKIT net product revenues -- -- Strengthening presence in allergy and inflammation with the IND for wild-type KIT inhibitor BLU-808 on track for filing in Q2 -- "We delivered another very strong quarter in our launch of AYVAKIT in indolent systemic mastocytosis (ISM) and have entered 2024 in a position of stren ...

Financial Data and Key Metrics Changes - Blueprint Medicines reported total revenues of $249.4 million for 2023, which includes $204.2 million in net product revenues from AYVAKIT and $45.2 million in collaboration and license revenues [52] - AYVAKIT achieved $204 million in global revenue in 2023, representing an 84% increase over 2022 [4][18] - The company provided 2024 revenue guidance for AYVAKIT of $360 million to $390 million, indicating a potential year-over-year growth of over 80% at the midpoint [15][53] Business Line Data and Key Metrics Changes - AYVAKIT's fourth-quarter revenues grew 30% quarter-on-quarter to $71 million, with $63.6 million generated in the U.S. [18] - Approximately 1,000 patients were reported to be on AYVAKIT therapy in the U.S. as of January 2024, marking a significant milestone in the product's launch [8] - The company expects to sustain growth in AYVAKIT driven by new patient starts, compliance, and duration of therapy [19][21] Market Data and Key Metrics Changes - The systemic mastocytosis (SM) market is expanding, with an estimated 70,000 prevalent patients in the U.S. and Europe [4] - The company anticipates that the ex-U.S. AYVAKIT revenue split in 2024 will be consistent with 2023, starting with a launch in Germany [53][90] - The company is focused on increasing awareness and activating patients to seek treatment, as many diagnosed patients are not well controlled on existing therapies [10] Company Strategy and Development Direction - Blueprint Medicines is focusing on three key areas: driving AYVAKIT's growth, advancing its portfolio targeting allergic inflammatory diseases, and maintaining a strong financial position [25][17] - The company aims to leverage its expertise in mast cell biology to develop therapies for various mast cell-driven inflammatory diseases [23] - Blueprint is also pursuing business development opportunities to optimize its operations sustainably, including a deal to ensure GAVRETO's availability while minimizing financial impact [7] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in AYVAKIT's potential to achieve peak global sales of over $2 billion, driven by strong underlying fundamentals and rapid growth in diagnosis [5][26] - The company is optimistic about the long-term efficacy and safety data from AYVAKIT, which is expected to establish it as the standard of care for systemic mastocytosis [33] - Management highlighted the importance of patient compliance and low discontinuation rates as positive indicators for the product's future revenue growth [117] Other Important Information - The company plans to showcase its developments at the upcoming AAAAI conference, emphasizing its leadership in SM science and medicine [6][33] - Blueprint Medicines is committed to maintaining a disciplined approach to capital allocation while investing in high-potential growth opportunities [55] Q&A Session Summary Question: What is the overall approach coming into guidance? - Management noted that they are still early in the launch and are understanding quarter-on-quarter dynamics, including seasonality impacts [57] Question: What are the key execution steps to increase patient starts? - The team emphasized targeting high-volume prescribers and leveraging data analytics to inform their promotional efforts [60] Question: How does the company view the differentiation of BLU-263 relative to AYVAKIT? - Management highlighted the robust data from the Phase 2 trial and the ongoing collection of scientific information to support differentiation [70] Question: What is the contribution of allergists to new prescriptions? - The contribution from allergists has increased to the mid-30s percentage, indicating strong engagement and motivation to prescribe AYVAKIT [126] Question: What is the trajectory for AYVAKIT in Europe? - The company is launching AYVAKIT in Germany first, with expectations for other markets to follow as pricing and reimbursement are negotiated [90]

PART I [Business Overview](index=10&type=section&id=Item%201.%20Business) Blueprint Medicines is a global biopharmaceutical company developing therapies in allergy/inflammation and oncology/hematology, leveraging kinase inhibition and targeted protein degradation platforms - **Blueprint Medicines is a fully-integrated, commercial-stage biopharmaceutical company focused on allergy/inflammation and oncology/hematology, utilizing kinase inhibition and targeted protein degradation**[145](index=145&type=chunk)[146](index=146&type=chunk) - **The company commercializes AYVAKIT®/AYVAKYT® (avapritinib) for systemic mastocytosis (SM) and PDGFRA Exon 18 mutant GIST in the U.S. and Europe**[145](index=145&type=chunk) - **The pipeline includes elenestinib (BLU-263) for indolent SM, BLU-808 for chronic urticaria, and BLU-222 for HR+/HER2- breast cancer and other solid tumors vulnerable to CDK2 inhibition**[145](index=145&type=chunk)[148](index=148&type=chunk)[223](index=223&type=chunk) [Overview](index=10&type=section&id=Overview) Blueprint Medicines is a global biopharmaceutical company focused on allergy/inflammation and oncology/hematology, using a drug discovery approach combining biological insights with proprietary research platforms - **Blueprint Medicines is a global biopharmaceutical company focused on allergy/inflammation and oncology/hematology, using a drug discovery approach combining biological insights with proprietary research platforms like kinase inhibition and targeted protein degradation**[145](index=145&type=chunk)[146](index=146&type=chunk) [Mast Cell-mediated Diseases — AYVAKIT®/AYVAKYT® (avapritinib), Elenestinib (BLU-263), and BLU-808](index=10&type=section&id=Mast%20Cell-mediated%20Diseases%20%E2%80%94%20AYVAKIT%C2%AE%2FAYVAKYT%C2%AE%20(avapritinib)%2C%20Elenestinib%20(BLU-263)%2C%20and%20BLU-808) The company is building a mast cell-mediated disease franchise, commercializing AYVAKIT/AYVAKYT and developing elenestinib and BLU-808 - **The company is building a mast cell-mediated disease franchise, commercializing AYVAKIT/AYVAKYT for advanced SM and indolent SM, and developing elenestinib (BLU-263) for indolent SM and BLU-808 for chronic urticaria**[148](index=148&type=chunk)[172](index=172&type=chunk) [Systemic Mastocytosis (SM)](index=12&type=section&id=Systemic%20Mastocytosis%20(SM)) Systemic Mastocytosis is a mast cell disorder characterized by a KIT D816V mutation, ranging from indolent to advanced forms with varying severity - **SM is a mast cell disorder, with approximately 95% of patients having a KIT D816V mutation, ranging from indolent SM with severe symptoms to advanced SM with organ dysfunction and reduced life expectancy**[203](index=203&type=chunk) - **Current treatments for non-advanced SM are symptom-directed, while advanced SM has limited approved targeted therapies other than AYVAKIT for KIT D816V mutation**[176](index=176&type=chunk)[204](index=204&type=chunk) [AYVAKIT®/AYVAKYT® (avapritinib)](index=12&type=section&id=AYVAKIT%C2%AE%2FAYVAKYT%C2%AE%20(avapritinib)) AYVAKIT/AYVAKYT is approved in the U.S. and EU for advanced and indolent systemic mastocytosis, and for PDGFRA Exon 18 mutant GIST - **AYVAKIT is approved by the FDA for advanced SM (June 2021) and indolent SM (May 2023), while AYVAKYT received EU marketing authorization for advanced SM (March 2022) and indolent SM (December 2023)**[177](index=177&type=chunk) - **Avapritinib also holds FDA approval for unresectable or metastatic GIST with PDGFRA exon 18 mutation, including D842V mutations, and has received Breakthrough Therapy and Orphan Drug designations for SM and GIST**[179](index=179&type=chunk)[206](index=206&type=chunk)[207](index=207&type=chunk) - **PIONEER Part 2 trial data showed significant improvements in patient-reported symptoms, with an ISM-SAF TSS reduction of 15.6 points at 24 weeks versus 9.2 for placebo (p=0.003), and mast cell burden, with 53.9% of AYVAKIT-treated patients achieving at least 50% serum tryptase reduction versus 0% for control (p<0.0001)**[210](index=210&type=chunk)[212](index=212&type=chunk) - **Pooled data from EXPLORER and PATHFINDER trials in advanced SM showed an 84% Overall Response Rate (ORR) in treatment-naïve patients and an estimated 24-month Overall Survival (OS) rate of 88%**[216](index=216&type=chunk) [Elenestinib (BLU-263)](index=16&type=section&id=Elenestinib%20(BLU-263)) Elenestinib (BLU-263) is an investigational, orally available, potent and highly selective KIT D816V inhibitor for indolent SM and other mast cell disorders - **Elenestinib (BLU-263) is an investigational, orally available, potent and highly selective KIT D816V inhibitor for indolent SM and other mast cell disorders, designed for lower CNS penetration than avapritinib**[148](index=148&type=chunk)[245](index=245&type=chunk) - **HARBOR Part 1 trial data showed dose-dependent reductions in patient-reported symptoms, with TSS reductions of 28.5% to 33.6% across doses versus 22.2% for control at 12 weeks, and objective measures of mast cell burden**[219](index=219&type=chunk) - **Elenestinib was generally well-tolerated in the HARBOR Part 1 trial, with most Adverse Events (AEs) reported as Grade 1–2 and no discontinuations due to AEs**[248](index=248&type=chunk) [BLU-808](index=16&type=section&id=BLU-808) BLU-808 is an oral, highly potent and selective wild-type KIT inhibitor nominated for mast cell disorders, including chronic urticaria, with an IND application planned for Q2 2024 - **BLU-808, an oral, highly potent and selective wild-type KIT inhibitor, was nominated as a development candidate in H1 2023 for mast cell disorders, including chronic urticaria**[249](index=249&type=chunk) - **The company plans to submit an Investigational New Drug (IND) application for BLU-808 in Q2 2024 and initiate a Phase 1 study in healthy volunteers**[221](index=221&type=chunk) [Oncology/Hematology](index=18&type=section&id=Oncology%2FHematology) Blueprint Medicines continues active discovery in oncology, planning to accelerate BLU-222 development and advance cell cycle research in 2024 - **Blueprint Medicines continues active discovery in oncology, with plans to accelerate development of BLU-222 and advance cell cycle research in 2024**[222](index=222&type=chunk) [HR+/HER2- Breast Cancer and Other Solid Tumors– BLU-222, BLU-956 and additional research programs](index=18&type=section&id=HR%2B%2FHER2-%20Breast%20Cancer%20and%20Other%20Solid%20Tumors%E2%80%93%20BLU-222%2C%20BLU-956%20and%20additional%20research%20programs) BLU-222, a CDK2 inhibitor, is in Phase 1/2 clinical trials for HR+/HER2- breast cancer and other CDK2-vulnerable cancers, showing a confirmed partial response - **BLU-222, a CDK2 inhibitor, is in Phase 1/2 VELA trial for HR+/HER2- breast cancer and other CDK2-vulnerable cancers, showing a confirmed partial response in a monotherapy-treated patient**[223](index=223&type=chunk)[252](index=252&type=chunk) - **The company is also advancing BLU-956, a next-generation CDK2 inhibitor, and a CDK2 targeted protein degradation research program**[223](index=223&type=chunk) [Solid Tumors: RET-Altered Cancers — GAVRETO® (pralsetinib)](index=18&type=section&id=Solid%20Tumors%3A%20RET-Altered%20Cancers%20%E2%80%94%20GAVRETO%C2%AE%20(pralsetinib)) Roche terminated its collaboration for GAVRETO (pralsetinib), leading Blueprint Medicines to seek a new U.S. partner and discontinue global development outside the U.S. and Greater China - **Roche terminated its collaboration agreement for GAVRETO (pralsetinib) in February 2023, effective February 2024, leading the company to seek a new U.S. commercialization partner and discontinue global development and marketing outside the U.S. and Greater China**[226](index=226&type=chunk)[259](index=259&type=chunk)[819](index=819&type=chunk)[821](index=821&type=chunk) - **GAVRETO was developed for RET fusion-positive Non-Small Cell Lung Cancer (NSCLC) and RET-altered thyroid carcinoma, with oncogenic RET alterations implicated in various cancers**[57](index=57&type=chunk)[253](index=253&type=chunk) [Solid Tumors: EGFR-Mutated NSCLC – BLU-945, BLU-451, and BLU-525](index=20&type=section&id=Solid%20Tumors%3A%20EGFR-Mutated%20NSCLC%20%E2%80%93%20BLU-945%2C%20BLU-451%2C%20and%20BLU-525) In January 2024, the company discontinued global investment in early clinical-stage EGFR inhibitors (BLU-945, BLU-451, BLU-525), exploring out-licensing options while Zai Lab retains rights in Greater China - **In January 2024, the company discontinued further investment in early clinical-stage EGFR inhibitors (BLU-945, BLU-451, BLU-525) globally, except for Zai Lab's rights in Greater China, and is exploring out-licensing options**[234](index=234&type=chunk)[236](index=236&type=chunk)[255](index=255&type=chunk) [Discovery Platform](index=20&type=section&id=Discovery%20Platform) The company's discovery platform identifies kinase drivers and is expanding into targeted protein degradation through internal programs and collaborations - **The company's discovery platform identifies kinase drivers in genomically defined patient populations and is expanding into targeted protein degradation for kinase and non-kinase targets through collaborations**[256](index=256&type=chunk) - **Six early degrader research programs were initiated since 2022, including four internal and two under the collaboration with Proteovant/VantAI**[58](index=58&type=chunk) [Collaborations and Licenses Summary](index=20&type=section&id=Collaborations%20and%20Licenses%20Summary) The company maintains collaborations with CStone, Zai Lab, VantAI, Clementia, and IDRx for the development and commercialization of various drug candidates - **The company has collaborations with CStone, Zai Lab, VantAI, Clementia, and IDRx for development and commercialization of various drug candidates**[31](index=31&type=chunk) [Roche – Immunotherapy Collaboration](index=26&type=section&id=Roche%20%E2%80%93%20Immunotherapy%20Collaboration) The immunotherapy collaboration with Roche was mutually terminated in April 2023, with Blueprint Medicines retaining rights to developed compounds and exploring re-partnering - **The immunotherapy collaboration with Roche was mutually terminated on April 30, 2023, with Blueprint Medicines retaining rights to all developed compounds and exploring re-partnering the asset**[231](index=231&type=chunk)[268](index=268&type=chunk) - **The company received an upfront payment of $45.0 million in March 2016 and $25.0 million in research milestones, while paying Roche $5.3 million for cost sharing on BLU-852 IND-enabling activities**[297](index=297&type=chunk) [Roche – Pralsetinib Collaboration](index=26&type=section&id=Roche%20%E2%80%93%20Pralsetinib%20Collaboration) Roche terminated the pralsetinib collaboration agreement effective February 2024, prompting Blueprint Medicines to seek a new U.S. commercialization partner and discontinue global development outside the U.S. and Greater China - **Roche provided written notice in February 2023 to terminate the pralsetinib collaboration agreement, effective February 22, 2024, leading the company to seek a new U.S. commercialization partner and discontinue global development and marketing outside the U.S. and Greater China**[226](index=226&type=chunk)[259](index=259&type=chunk)[819](index=819&type=chunk)[821](index=821&type=chunk) - **Under the agreement, Blueprint Medicines received $775.0 million upfront, including a $100.0 million equity investment, and $105.0 million in regulatory and commercialization milestones through December 31, 2023**[298](index=298&type=chunk) [CStone](index=26&type=section&id=CStone) The collaboration with CStone Pharmaceuticals grants exclusive rights to develop and commercialize avapritinib, pralsetinib, and fisogatinib in Greater China - **Collaboration with CStone Pharmaceuticals grants exclusive rights to develop and commercialize avapritinib, pralsetinib, and fisogatinib in Greater China**[233](index=233&type=chunk)[299](index=299&type=chunk) - **Blueprint Medicines received $40.0 million upfront and $38.5 million in milestone payments through December 31, 2023, with eligibility for up to $307.5 million in future contingent payments and tiered royalties**[270](index=270&type=chunk)[789](index=789&type=chunk) [Clementia](index=28&type=section&id=Clementia) The license agreement with Clementia Pharmaceuticals for BLU-782 (fidrisertib) for fibrodysplasia ossificans progressiva (FOP) includes Rare Pediatric Disease, Orphan Drug, and Fast Track designations - **License agreement with Clementia Pharmaceuticals for BLU-782 (fidrisertib) for fibrodysplasia ossificans progressiva (FOP), which has Rare Pediatric Disease, Orphan Drug, and Fast Track designations**[32](index=32&type=chunk)[261](index=261&type=chunk) - **Blueprint Medicines received $25.0 million upfront and $50.0 million in milestone payments through December 31, 2023, with eligibility for up to $460.0 million in future milestones and tiered royalties**[272](index=272&type=chunk) [Zai Lab](index=30&type=section&id=Zai%20Lab) The collaboration with Zai Lab for BLU-945 and BLU-525 for EGFR-driven NSCLC in Greater China continues, despite Blueprint Medicines discontinuing global investment in these therapies - **Collaboration with Zai Lab for BLU-945 and BLU-525 for EGFR-driven NSCLC in Greater China, with Zai Lab retaining rights despite Blueprint Medicines discontinuing global investment in these therapies**[234](index=234&type=chunk)[306](index=306&type=chunk)[790](index=790&type=chunk) - **Blueprint Medicines received $25.0 million upfront and is eligible for up to $590.0 million in contingent payments and tiered royalties**[275](index=275&type=chunk)[1403](index=1403&type=chunk) [VantAI](index=30&type=section&id=VantAI) The amended collaboration with VantAI focuses on researching and advancing three novel protein degrader programs, with an option for a fourth - **Amended and Restated Collaboration and License Agreement with VantAI (replacing Proteovant) to research and advance three novel protein degrader programs, with an option for a fourth**[58](index=58&type=chunk)[262](index=262&type=chunk)[276](index=276&type=chunk)[307](index=307&type=chunk)[1400](index=1400&type=chunk) - **VantAI is eligible for up to $1.67 billion in contingent payments, including research, development, regulatory, and commercialization milestones, and tiered mid-single digit royalties on net sales**[823](index=823&type=chunk)[1371](index=1371&type=chunk) [IDRx](index=32&type=section&id=IDRx) The license agreement with IDRx for IDRX-73, a KIT exon 13 inhibitor, provides Blueprint Medicines with Series A preferred stock and anti-dilution rights - **License agreement with IDRx for IDRX-73, a KIT exon 13 inhibitor, where Blueprint Medicines received 4,509,105 shares of IDRx's Series A preferred stock and has anti-dilution rights**[59](index=59&type=chunk)[63](index=63&type=chunk)[235](index=235&type=chunk)[310](index=310&type=chunk)[1364](index=1364&type=chunk) - **Blueprint Medicines is eligible for up to $217.5 million in contingent cash payments, including development, regulatory, and sales milestones, and tiered royalties up to low-teens on net sales**[235](index=235&type=chunk)[310](index=310&type=chunk)[1394](index=1394&type=chunk) [Mergers & Acquisitions Summary](index=23&type=section&id=Mergers%20%26%20Acquisitions%20Summary) This section summarizes the company's mergers and acquisitions activities [Lengo Therapeutics](index=32&type=section&id=Lengo%20Therapeutics) Blueprint Medicines acquired Lengo Therapeutics in December 2021 for $250.0 million upfront, gaining LNG-451 (BLU-451) for EGFR exon 20 insertion mutations in NSCLC, but discontinued further investment in January 2024 - **Acquired Lengo Therapeutics in December 2021 for $250.0 million upfront, gaining LNG-451 (BLU-451) for EGFR exon 20 insertion mutations in NSCLC**[236](index=236&type=chunk)[278](index=278&type=chunk)[312](index=312&type=chunk)[1470](index=1470&type=chunk) - **In January 2024, the company discontinued further investment in BLU-451 and is exploring strategic options, including out-licensing**[236](index=236&type=chunk)[278](index=278&type=chunk)[1399](index=1399&type=chunk) [Financing Arrangement Summary](index=23&type=section&id=Financing%20Arrangement%20Summary) This section summarizes the company's financing arrangements [Synthetic Royalty Facility](index=34&type=section&id=Synthetic%20Royalty%20Facility) In June 2022, the company entered a Future Revenue Purchase Agreement with Sixth Street Partners, receiving $250.0 million for future royalties on AYVAKIT/AYVAKYT and elenestinib sales - **In June 2022, the company entered a Future Revenue Purchase Agreement with Sixth Street Partners, receiving $250.0 million for future royalties on AYVAKIT/AYVAKYT and elenestinib sales, excluding Greater China**[237](index=237&type=chunk)[314](index=314&type=chunk) - **The royalty rate is 9.75% on up to $900 million annually, subject to a cumulative cap of 1.45 times invested capital ($362.5 million), with potential increases to 15% and 1.85 times ($462.5 million) if revenue targets are not met**[237](index=237&type=chunk)[314](index=314&type=chunk) [Debt Facility](index=34&type=section&id=Debt%20Facility) In June 2022, the company secured a financing agreement for up to $660.0 million with Sixth Street Partners, including a $150.0 million senior secured term loan and a $250.0 million delayed draw term loan facility - **In June 2022, the company secured a financing agreement for up to $660.0 million with Sixth Street Partners, including a $150.0 million senior secured term loan drawn in July 2022 and a $250.0 million delayed draw term loan facility**[281](index=281&type=chunk)[292](index=292&type=chunk) - **Received $100.0 million from the first tranche of the delayed draw term loan in August 2023, with loans maturing June 30, 2028, at variable interest rates (SOFR + 6.50% or base rate + 5.50%)**[281](index=281&type=chunk)[292](index=292&type=chunk) [Our Strategy](index=24&type=section&id=Our%20Strategy) The company's strategy focuses on accelerating adoption of approved medicines, expanding global commercial capabilities, deepening focus on mast cell-mediated diseases, advancing innovative research programs, and evaluating new collaborations - **Key strategic elements include accelerating adoption of approved medicines, expanding global commercial capabilities, deepening focus on mast cell-mediated diseases, advancing innovative research programs such as BLU-222, and evaluating new collaborations**[238](index=238&type=chunk)[239](index=239&type=chunk)[266](index=266&type=chunk)[294](index=294&type=chunk) [Intellectual Property](index=34&type=section&id=Intellectual%20Property) The company protects its intellectual property through U.S. and international patents, trademarks, trade secrets, and know-how for its drugs, drug candidates, and discovery platforms - **The company protects its intellectual property through U.S. and international patents, trademarks, trade secrets, and know-how for its drugs, drug candidates, and discovery platforms**[315](index=315&type=chunk)[750](index=750&type=chunk) [AYVAKIT/AYVAKYT (avapritinib)](index=36&type=section&id=AYVAKIT%2FAYVAKYT%20(avapritinib)) The patent portfolio for AYVAKIT/AYVAKYT includes U.S., European, and other foreign patents, with various FDA and EMA exclusivities extending to 2030 and beyond - **The patent portfolio includes 5 U.S. patents, 3 European patents, and 24 other foreign patents, with statutory expiration dates between 2034 and 2043**[284](index=284&type=chunk) - **The FDA granted New Chemical Entity (NCE) exclusivity until January 9, 2025, and Orphan Drug Exclusivity (ODE) until January 9, 2027, with additional ODEs and new clinical indication exclusivities extending to 2030**[346](index=346&type=chunk) - **The EMA granted AYVAKYT Orphan marketing exclusivity until September 25, 2030, and December 12, 2032, for different approvals, with market protection until September 25, 2031**[825](index=825&type=chunk) [GAVRETO (pralsetinib)](index=36&type=section&id=GAVRETO%20(pralsetinib)) The patent portfolio for GAVRETO includes U.S. and foreign patents, with FDA and EMA exclusivities extending to 2027 and 2031 respectively - **The patent portfolio includes 4 U.S. patents and 34 foreign patents, with statutory expiration dates between 2036 and 2041**[285](index=285&type=chunk) - **The FDA granted New Chemical Entity (NCE) exclusivity until September 4, 2025, and Orphan Drug Exclusivity (ODE) until September 4, 2027, with additional ODEs until December 1, 2027**[347](index=347&type=chunk) - **The EMA granted GAVRETO data exclusivity until November 22, 2029, and marketing protection until November 22, 2031**[319](index=319&type=chunk) [KIT Program—Elenestinib](index=36&type=section&id=KIT%20Program%E2%80%94Elenestinib) The patent portfolio for the KIT program, including elenestinib, contains U.S. and foreign patents and pending applications, with statutory expiration dates between 2034 and 2043 - **The patent portfolio for the KIT program, including elenestinib, contains 8 U.S. patents, 1 foreign patent, and pending applications, with statutory expiration dates between 2034 and 2043**[65](index=65&type=chunk) [CDK2 Program](index=38&type=section&id=CDK2%20Program) The patent portfolio for the CDK2 program, including BLU-222, contains 65 pending patent applications, with statutory expiration dates between 2042 and 2044 - **The patent portfolio for the CDK2 program, including BLU-222, contains 65 pending patent applications, with statutory expiration dates between 2042 and 2044**[287](index=287&type=chunk) [MAP4K1 Program](index=38&type=section&id=MAP4K1%20Program) The patent portfolio for the MAP4K1 program, including BLU-852, contains one U.S. patent and pending applications, with statutory expiration dates between 2041 and 2042 - **The patent portfolio for the MAP4K1 program, including BLU-852, contains one U.S. patent and pending applications, with statutory expiration dates between 2041 and 2042**[321](index=321&type=chunk) [Other Considerations](index=38&type=section&id=Other%20Considerations) The company relies on unpatented trade secrets and know-how for its proprietary compound library and targeted protein degrader platform as primary intellectual property assets - **The company relies on unpatented trade secrets and know-how for its proprietary compound library and targeted protein degrader platform, which are primary intellectual property assets**[323](index=323&type=chunk)[351](index=351&type=chunk) [Competition](index=40&type=section&id=Competition) The pharmaceutical and biotechnology industries are highly competitive, with numerous companies developing therapies in kinase inhibition for cancer and rare diseases - **The pharmaceutical and biotechnology industries are highly competitive, with numerous companies developing therapies in kinase inhibition for cancer and rare diseases**[324](index=324&type=chunk)[353](index=353&type=chunk) - **Competitors often have greater financial resources and expertise in research and development, manufacturing, clinical trials, regulatory approvals, and marketing**[66](index=66&type=chunk)[331](index=331&type=chunk) [SM](index=40&type=section&id=SM) AYVAKIT/AYVAKYT and elenestinib face competition for advanced SM from Novartis AG's midostaurin and imatinib, and from drug candidates by Cogent Biosciences, Inc. and Hoth Therapeutics - **AYVAKIT/AYVAKYT and elenestinib face competition for advanced SM from Novartis AG's midostaurin and imatinib, and from drug candidates by Cogent Biosciences, Inc. and Hoth Therapeutics**[326](index=326&type=chunk) - **For non-advanced SM, competition includes drug candidates from AB Science S.A., Allakos Inc., Cogent Biosciences, Inc., Hoth Therapeutics, Invea Therapeutics Inc., and Theseus Pharmaceuticals Inc.**[326](index=326&type=chunk) [Chronic Urticaria](index=40&type=section&id=Chronic%20Urticaria) BLU-808 for chronic urticaria will compete with Genentech and Novartis' omalizumab and numerous drug candidates from other companies - **BLU-808 for chronic urticaria will compete with Genentech and Novartis' omalizumab and numerous drug candidates from other companies**[327](index=327&type=chunk)[328](index=328&type=chunk) [HR+/HER2- Breast Cancer and Other Cancers Vulnerable to CDK2 Inhibition](index=42&type=section&id=HR%2B%2FHER2-%20Breast%20Cancer%20and%20Other%20Cancers%20Vulnerable%20to%20CDK2%20Inhibition) BLU-222 for CDK2-vulnerable cancers faces competition from indication-specific therapies like AstraZeneca's capivasertib and Merck's olaparib, as well as many drug candidates in development - **BLU-222 for CDK2-vulnerable cancers faces competition from indication-specific therapies like AstraZeneca's capivasertib and Merck's olaparib, as well as many drug candidates in development**[329](index=329&type=chunk) [RET-Altered Cancers](index=42&type=section&id=RET-Altered%20Cancers) GAVRETO faces competition for RET fusion-positive NSCLC from Eli Lilly and Company's selpercatinib and other drug candidates in development - **GAVRETO faces competition for RET fusion-positive Non-Small Cell Lung Cancer (NSCLC) from Eli Lilly and Company's selpercatinib and other drug candidates in development**[67](index=67&type=chunk) [GIST](index=42&type=section&id=GIST) AYVAKIT/AYVAKYT faces competition from drug candidates in development for PDGFRA-driven GIST, including those from AB Science S.A., ARIAD Pharmaceuticals, Inc., and Cogent Biosciences, Inc. - **AYVAKIT/AYVAKYT faces competition from drug candidates in development for PDGFRA-driven GIST, including those from AB Science S.A., ARIAD Pharmaceuticals, Inc., and Cogent Biosciences, Inc.**[330](index=330&type=chunk) [Commercialization](index=42&type=section&id=Commercialization) The company's strategy focuses on efficiently commercializing approved drugs in the U.S. and Europe using a specialized sales force, with plans to expand globally and evaluate collaborations - **The company's strategy focuses on efficiently commercializing approved drugs in the U.S. and Europe using a specialized sales force, with plans to expand globally and evaluate collaborations**[331](index=331&type=chunk)[359](index=359&type=chunk) [Manufacturing and Supply](index=44&type=section&id=Manufacturing%20and%20Supply) The company relies on single-source third-party manufacturers for preclinical, clinical, and commercial supply of its small molecule drugs, which are produced via reproducible synthetic processes - **The company relies on single-source third-party manufacturers for preclinical, clinical, and commercial supply of its small molecule drugs, which are produced via reproducible synthetic processes**[333](index=333&type=chunk)[361](index=361&type=chunk) [Government Regulation](index=44&type=section&id=Government%20Regulation) Drug development, testing, manufacturing, approval, labeling, marketing, and distribution are extensively regulated by government authorities in the U.S. and other countries - **Drug development, testing, manufacturing, approval, labeling, marketing, and distribution are extensively regulated by government authorities in the U.S. and other countries**[362](index=362&type=chunk) [U.S. Drug Development](index=44&type=section&id=U.S.%20Drug%20Development) The FDA regulates drugs under the FDCA, requiring extensive preclinical tests and human clinical trials before marketing approval, with an IND application required before human trials begin - **The FDA regulates drugs under the Federal Food, Drug, and Cosmetic Act (FDCA), requiring extensive preclinical tests (GLP-compliant) and human clinical trials (GCP-compliant) before marketing approval**[335](index=335&type=chunk)[336](index=336&type=chunk)[363](index=363&type=chunk)[398](index=398&type=chunk) - **An Investigational New Drug (IND) application must be effective before human trials begin, and clinical trials are typically conducted in three phases (Phase 1, 2, 3)**[336](index=336&type=chunk)[363](index=363&type=chunk)[366](index=366&type=chunk) [NDA and FDA Review Process](index=48&type=section&id=NDA%20and%20FDA%20Review%20Process) After clinical trials, results are submitted to the FDA as a New Drug Application (NDA), requiring extensive evidence of safety, efficacy, manufacturing information, and cGMP compliance - **After clinical trials, results are submitted to the FDA as a New Drug Application (NDA), requiring extensive evidence of safety and efficacy, manufacturing information, and compliance with current Good Manufacturing Practices (cGMP)**[368](index=368&type=chunk) - **The FDA reviews NDAs for safety, efficacy, and cGMP compliance, potentially referring applications to advisory committees, with approval possibly limited or requiring post-marketing studies**[341](index=341&type=chunk)[370](index=370&type=chunk)[371](index=371&type=chunk)[831](index=831&type=chunk) [Special FDA Expedited Review and Approval Programs](index=52&type=section&id=Special%20FDA%20Expedited%20Review%20and%20Approval%20Programs) The FDA offers expedited programs like Fast Track, Accelerated Approval, Priority Review, and Breakthrough Therapy designation for serious or life-threatening conditions with unmet medical needs - **The FDA offers expedited programs like Fast Track, Accelerated Approval, Priority Review, and Breakthrough Therapy designation for serious or life-threatening conditions with unmet medical needs**[372](index=372&type=chunk)[373](index=373&type=chunk)[405](index=405&type=chunk)[406](index=406&type=chunk) - **Accelerated approval may be based on surrogate endpoints, requiring post-marketing studies, and the Food and Drug Omnibus Reform Act (FDORA) grants the FDA increased authority to withdraw accelerated approvals if confirmatory trials fail**[373](index=373&type=chunk)[630](index=630&type=chunk) - **A platform technology can be designated for expedited development and review if it shows potential for multiple drugs without adverse effects and brings significant efficiencies**[407](index=407&type=chunk)[599](index=599&type=chunk)[628](index=628&type=chunk) [Pediatric Trials](index=54&type=section&id=Pediatric%20Trials) New Drug Applications (NDAs) must include pediatric data or a Pediatric Study Plan (PSP), which can be deferred or waived under certain conditions - **New Drug Applications (NDAs) must include pediatric data or a Pediatric Study Plan (PSP), which can be deferred or waived under certain conditions**[369](index=369&type=chunk)[377](index=377&type=chunk) [Post-Marketing Requirements](index=54&type=section&id=Post-Marketing%20Requirements) Approved drugs are subject to ongoing FDA regulation, including monitoring, recordkeeping, adverse event reporting, and compliance with cGMP for manufacturing - **Approved drugs are subject to ongoing FDA regulation, including monitoring, recordkeeping, adverse event reporting, and compliance with current Good Manufacturing Practices (cGMP) for manufacturing**[378](index=378&type=chunk)[410](index=410&type=chunk) - **Post-approval commitments may include Phase 4 clinical trials, Risk Evaluation and Mitigation Strategies (REMS), and surveillance, with non-compliance potentially leading to severe penalties, including market withdrawal**[380](index=380&type=chunk)[412](index=412&type=chunk)[671](index=671&type=chunk) [Other Regulatory Matters](index=56&type=section&id=Other%20Regulatory%20Matters) Manufacturing, sales, and promotion are regulated by various U.S. federal and state authorities, including compliance with fraud and abuse laws, Medicaid rebate requirements, and the 340B drug pricing program - **Manufacturing, sales, and promotion are regulated by various U.S. federal and state authorities, including compliance with fraud and abuse laws, Medicaid rebate requirements, and the 340B drug pricing program**[382](index=382&type=chunk) [U.S. Patent Term Restoration and Marketing Exclusivity](index=58&type=section&id=U.S.%20Patent%20Term%20Restoration%20and%20Marketing%20Exclusivity) The Hatch-Waxman Amendments allow up to five years of patent term restoration for FDA-approved drugs, with marketing exclusivity provisions delaying generic applications - **The Hatch-Waxman Amendments allow up to five years of patent term restoration for FDA-approved drugs, compensating for regulatory review time, with a maximum total term of 14 years from approval**[416](index=416&type=chunk) - **Marketing exclusivity provisions include five years for new chemical entities (NCE) and three years for new clinical investigations, delaying generic applications**[385](index=385&type=chunk) [Orphan Drug Designation](index=58&type=section&id=Orphan%20Drug%20Designation) Orphan drug designation is granted for drugs treating rare diseases, providing financial incentives and seven years of market exclusivity upon first approval, though exclusivity can be lost under certain conditions - **Orphan drug designation is granted for drugs treating rare diseases (fewer than 200,000 U.S. patients or insufficient sales recovery), providing financial incentives and seven years of market exclusivity upon first approval**[386](index=386&type=chunk)[388](index=388&type=chunk)[633](index=633&type=chunk)[634](index=634&type=chunk) - **Exclusivity can be lost if a later drug is clinically superior, if the designation request was materially defective, or if sufficient drug quantity cannot be assured**[607](index=607&type=chunk)[637](index=637&type=chunk) [Rare Pediatric Disease Designation and Priority Review Vouchers](index=60&type=section&id=Rare%20Pediatric%20Disease%20Designation%20and%20Priority%20Review%20Vouchers) Drugs for rare pediatric diseases may be eligible for a Priority Review Voucher (PRV) upon NDA approval, which can be sold or transferred - **Drugs for rare pediatric diseases, affecting patients aged 0-18 years and fewer than 200,000 U.S. patients, may be eligible for a Priority Review Voucher (PRV) upon New Drug Application (NDA) approval, which can be sold or transferred**[390](index=390&type=chunk) [European Union Drug Development](index=60&type=section&id=European%20Union%20Drug%20Development) The EU's Clinical Trials Regulation (EU) No 536/2014, effective January 31, 2022, streamlines clinical trial approval with a single entry point and defined deadlines - **The EU's Clinical Trials Regulation (EU) No 536/2014, effective January 31, 2022, streamlines clinical trial approval with a single entry point and defined deadlines**[421](index=421&type=chunk) [Drug Review and Approval](index=62&type=section&id=Drug%20Review%20and%20Approval) EU marketing authorizations can be centralized through the EMA or national through Member States, with the centralized procedure mandatory for certain products like orphan drugs - **EU marketing authorizations (MAs) can be centralized through the European Medicines Agency (EMA), valid across the EU/EEA, or national through Member States, with the centralized procedure mandatory for certain products like orphan drugs**[393](index=393&type=chunk)[450](index=450&type=chunk) - **Post-Brexit, Great Britain is no longer covered by centralized MAs, but the Medicines and Healthcare products Regulatory Agency (MHRA) may consider EMA approval decisions under a new international recognition framework**[451](index=451&type=chunk) [Pediatric Investigation Plan](index=62&type=section&id=Pediatric%20Investigation%20Plan) Marketing Authorization Applications (MAAs) in the EU must include results of pediatric studies in compliance with a Pediatric Investigation Plan (PIP), which can be deferred or waived by the EMA's Pediatric Committee (PDCO) - **Marketing Authorization Applications (MAAs) in the EU must include results of pediatric studies in compliance with a Pediatric Investigation Plan (PIP), which can be deferred or waived by the EMA's Pediatric Committee (PDCO)**[394](index=394&type=chunk) [Data and Market Exclusivity](index=64&type=section&id=Data%20and%20Market%20Exclusivity) Innovative medicinal products in the EU receive eight years of data exclusivity and an additional two years of market exclusivity, extendable to 11 years for new therapeutic indications with significant clinical benefit - **Innovative medicinal products in the EU receive eight years of data exclusivity and an additional two years of market exclusivity, extendable to 11 years for new therapeutic indications with significant clinical benefit**[453](index=453&type=chunk) - **Orphan medicinal products in the EU receive ten years of market exclusivity, which can be reduced to six years if criteria are no longer met or the product becomes sufficiently profitable**[396](index=396&type=chunk)[454](index=454&type=chunk) [Regulatory Requirements After a Marketing Authorization has been Obtained](index=64&type=section&id=Regulatory%20Requirements%20After%20a%20Marketing%20Authorization%20has%20been%20Obtained) Post-Marketing Authorization (MA), companies must comply with EU pharmacovigilance rules, cGMP standards for manufacturing, and strict regulations on marketing and promotion, including a prohibition on direct-to-consumer advertising for prescription medicines - **Post-Marketing Authorization (MA), companies must comply with EU pharmacovigilance rules, current Good Manufacturing Practices (cGMP) standards for manufacturing, and strict regulations on marketing and promotion, including a prohibition on direct-to-consumer advertising for prescription medicines**[397](index=397&type=chunk)[429](index=429&type=chunk)[455](index=455&type=chunk) [Reform of the Regulatory Framework in the European Union](index=66&type=section&id=Reform%20of%20the%20Regulatory%20Framework%20in%20the%20European%20Union) The UK's exit from the EU and the subsequent Trade and Cooperation Agreement mean the UK regulatory system is independent, potentially leading to divergence from EU regulations - **The UK's exit from the EU (Brexit) and the subsequent Trade and Cooperation Agreement (TCA) mean the UK regulatory system is independent, potentially leading to divergence from EU regulations**[430](index=430&type=chunk) - **The Windsor Framework, approved March 2023 and effective January 2025, will establish a single UK-wide marketing authorization by the Medicines and Healthcare products Regulatory Agency (MHRA), replacing the EU's role for Northern Ireland**[459](index=459&type=chunk) [Rest of the World Regulation](index=66&type=section&id=Rest%20of%20the%20World%20Regulation) Regulatory requirements for clinical trials, drug licensing, pricing, and reimbursement vary widely across countries outside the EU and U.S., requiring compliance with local GCPs and ethical principles - **Regulatory requirements for clinical trials, drug licensing, pricing, and reimbursement vary widely across countries outside the EU and U.S., requiring compliance with local Good Clinical Practices (GCPs) and ethical principles**[460](index=460&type=chunk) [Data Privacy and Security Laws](index=68&type=section&id=Data%20Privacy%20and%20Security%20Laws) The company is subject to global data protection laws, including GDPR, Swiss data protection laws, and U.S. state laws, which impose strict obligations on personal data processing and transfers - **The company is subject to global data protection laws, including GDPR (EU/UK), Swiss data protection laws, and U.S. state laws like CCPA/CPRA, which impose strict obligations on personal data processing and transfers**[69](index=69&type=chunk)[70](index=70&type=chunk)[71](index=71&type=chunk)[72](index=72&type=chunk)[101](index=101&type=chunk)[160](index=160&type=chunk)[435](index=435&type=chunk)[462](index=462&type=chunk)[798](index=798&type=chunk)[799](index=799&type=chunk)[801](index=801&type=chunk)[803](index=803&type=chunk)[862](index=862&type=chunk)[863](index=863&type=chunk) - **Non-compliance with these laws can result in significant fines, governmental investigations, litigation, and reputational harm**[69](index=69&type=chunk)[160](index=160&type=chunk)[435](index=435&type=chunk)[804](index=804&type=chunk)[862](index=862&type=chunk) - **Cybersecurity threats are an ongoing concern, with the company maintaining an information security team and processes to manage risks, including vendor risk assessments and penetration testing**[103](index=103&type=chunk)[463](index=463&type=chunk)[852](index=852&type=chunk) [Coverage and Reimbursement](index=70&type=section&id=Coverage%20and%20Reimbursement) Sales of drugs depend on third-party payor coverage and adequate reimbursement levels, which vary and are subject to cost-containment efforts and government program requirements - **Sales of drugs depend on third-party payor coverage, including government, commercial insurance, and managed care, and adequate reimbursement levels, which vary and are subject to cost-containment efforts**[437](index=437&type=chunk)[465](index=465&type=chunk)[469](index=469&type=chunk)[470](index=470&type=chunk) - **U.S. government programs like Medicaid and Medicare Part D have specific rebate and pricing requirements, such as the 340B drug pricing program, which can impact net revenue**[439](index=439&type=chunk)[440](index=440&type=chunk)[467](index=467&type=chunk)[469](index=469&type=chunk) - **Foreign countries often impose price controls and reimbursement restrictions, which can delay commercial launch and negatively impact revenues**[441](index=441&type=chunk)[503](index=503&type=chunk) [Healthcare Reform](index=73&type=section&id=Healthcare%20Reform) Healthcare reform measures, including the Affordable Care Act and the Inflation Reduction Act of 2022, and increasing governmental scrutiny over drug pricing, could adversely affect the business - **The Affordable Care Act (ACA) significantly impacted healthcare, increasing Medicaid rebates and establishing annual fees on branded prescription drugs**[498](index=498&type=chunk) - **The Inflation Reduction Act of 2022 (IRA) includes provisions for Medicare Part D out-of-pocket caps, manufacturer financial liability, government drug price negotiation, and inflation-based rebates, with potential impacts on the business**[472](index=472&type=chunk) - **There is increasing governmental scrutiny over drug pricing practices, leading to legislative initiatives and executive orders aimed at reducing prescription drug costs**[502](index=502&type=chunk) [Other Healthcare Laws](index=75&type=section&id=Other%20Healthcare%20Laws) The company is subject to federal and state anti-kickback, false claims, privacy, and consumer protection laws, which regulate business practices and can result in significant penalties for non-compliance - **The company is subject to federal and state anti-kickback, false claims, privacy (HIPAA, HITECH), and consumer protection laws, which regulate business practices and can result in significant penalties for non-compliance**[479](index=479&type=chunk)[480](index=480&type=chunk)[505](index=505&type=chunk)[506](index=506&type=chunk)[507](index=507&type=chunk)[510](index=510&type=chunk)[685](index=685&type=chunk) - **The Physician Payment Sunshine Act requires reporting of payments to physicians and teaching hospitals, with failure to comply resulting in civil monetary penalties**[481](index=481&type=chunk)[483](index=483&type=chunk) [Human Capital Resources](index=79&type=section&id=Human%20Capital%20Resources) As of January 31, 2024, the company had 655 global employees, with 367 in R&D and 208 holding advanced degrees, focusing on attracting and retaining talent through competitive compensation and development programs - **As of January 31, 2024, the company had 655 full- and part-time employees globally, with 367 engaged in research and development and 208 holding advanced degrees**[485](index=485&type=chunk) - **The company focuses on attracting and retaining talent through competitive compensation, comprehensive benefits, and professional development programs**[511](index=511&type=chunk) [Corporate Information](index=79&type=section&id=Corporate%20Information) Blueprint Medicines Corporation was incorporated in Delaware in October 2008 and is headquartered in Cambridge, Massachusetts - **Blueprint Medicines Corporation was incorporated in Delaware in October 2008 and is headquartered in Cambridge, Massachusetts**[487](index=487&type=chunk) [Information Available on the Internet](index=81&type=section&id=Information%20Available%20on%20the%20Internet) The company makes its SEC filings and other material information available on its website and through social media channels - **The company makes its SEC filings and other material information available on its website (www.blueprintmedicines.com) and through social media channels**[488](index=488&type=chunk)[515](index=515&type=chunk) [Risk Factors](index=81&type=section&id=Item%201A.%20Risk%20Factors) This section details significant risks across commercialization, drug development, regulatory compliance, third-party reliance, intellectual property, operations, and financial stability - **The company faces inherent risks across its operations, including commercialization, drug development, regulatory compliance, third-party reliance, intellectual property, and financial stability**[516](index=516&type=chunk) [Risks Related to Commercialization](index=81&type=section&id=Risks%20Related%20to%20Commercialization) The company faces risks in commercializing its drugs, including market acceptance, pricing, side effects, competition, and product liability lawsuits - **As a growing commercial company, the marketing and sales of AYVAKIT/AYVAKYT or future approved drugs may be unsuccessful due to factors like market acceptance, pricing, side effects, and competition**[33](index=33&type=chunk)[493](index=493&type=chunk)[517](index=517&type=chunk)[521](index=521&type=chunk) - **Market opportunities for approved drugs or candidates may be smaller than estimated, or approvals may be for narrower patient populations, adversely affecting revenue and profitability**[9](index=9&type=chunk)[525](index=525&type=chunk)[526](index=526&type=chunk) - **Substantial competition from major pharmaceutical and biotechnology companies with greater resources could reduce or limit commercial opportunities**[34](index=34&type=chunk)[66](index=66&type=chunk)[527](index=527&type=chunk)[531](index=531&type=chunk) - **Product liability lawsuits related to clinical trials or commercialized drugs could result in substantial liabilities, reputational harm, and limit commercialization**[22](index=22&type=chunk)[533](index=533&type=chunk) - **Increasing demand for compassionate use of drug candidates could negatively affect reputation and business, especially if supply is limited or adverse events occur**[534](index=534&type=chunk)[535](index=535&type=chunk)[555](index=555&type=chunk)[556](index=556&type=chunk) [Risks Related to Drug Development and Regulatory Approval](index=91&type=section&id=Risks%20Related%20to%20Drug%20Development%20and%20Regulatory%20Approval) The company faces significant risks in drug development and regulatory approval, including delays in clinical trials, unpredictable outcomes, undesirable side effects, and challenges in maintaining orphan drug designation - **Failure to advance drug candidates to clinical development, obtain regulatory approval, or commercialize them, or significant delays, would materially harm the business**[10](index=10&type=chunk)[23](index=23&type=chunk)[540](index=540&type=chunk)[561](index=561&type=chunk)[580](index=580&type=chunk) - **Delays or difficulties in patient enrollment for clinical trials, especially for rare diseases, could delay or or prevent regulatory approvals**[35](index=35&type=chunk)[563](index=563&type=chunk)[584](index=584&type=chunk)[585](index=585&type=chunk)[586](index=586&type=chunk) - **Preclinical and early clinical trial results may not predict later-stage outcomes, and interim data are subject to change, potentially harming business prospects**[36](index=36&type=chunk)[593](index=593&type=chunk)[622](index=622&type=chunk) - **Undesirable side effects from drugs or drug candidates could delay or prevent approval, limit commercial labels, or lead to market withdrawal and significant negative consequences**[11](index=11&type=chunk)[595](index=595&type=chunk)[597](index=597&type=chunk)[598](index=598&type=chunk)[624](index=624&type=chunk) - **Expedited review designations, such as Fast Track and Breakthrough Therapy, do not guarantee faster development or approval, nor do they increase the likelihood of marketing approval**[376](index=376&type=chunk)[601](index=601&type=chunk)[602](index=602&type=chunk) - **Failure to obtain or maintain orphan drug designation benefits, including market exclusivity, could expose drugs to competition**[605](index=605&type=chunk)[607](index=607&type=chunk)[634](index=634&type=chunk) - **The company may not successfully expand its pipeline of drug candidates or may misallocate resources to less profitable opportunities**[24](index=24&type=chunk)[611](index=611&type=chunk)[612](index=612&type=chunk)[638](index=638&type=chunk)[639](index=639&type=chunk)[640](index=640&type=chunk)[667](index=667&type=chunk) - **Developing drug candidates in combination with other therapies exposes the company to additional risks, including regulatory approval and supply issues for the combination agents**[615](index=615&type=chunk)[642](index=642&type=chunk)[643](index=643&type=chunk)[668](index=668&type=chunk) [Risks Related to Government Legislations and Regulations](index=108&type=section&id=Risks%20Related%20to%20Government%20Legislations%20and%20Regulations) The company faces risks from ongoing regulatory requirements, unfavorable pricing and reimbursement policies, healthcare reform measures, and compliance with various healthcare laws - **Ongoing and comprehensive regulatory requirements for approved drugs, including confirmatory trials for accelerated approvals, could lead to labeling restrictions, market withdrawal, or penalties for non-compliance**[12](index=12&type=chunk)[38](index=38&type=chunk)[669](index=669&type=chunk)[671](index=671&type=chunk) - **Unfavorable pricing regulations or third-party coverage and reimbursement policies could harm the business by limiting market access and revenue generation**[647](index=647&type=chunk)[649](index=649&type=chunk)[674](index=674&type=chunk)[675](index=675&type=chunk)[676](index=676&type=chunk) - **Healthcare reform measures, including federal and state initiatives to contain costs and control drug pricing, could adversely affect business and results of operations**[498](index=498&type=chunk)[502](index=502&type=chunk)[503](index=503&type=chunk)[678](index=678&type=chunk)[679](index=679&type=chunk)[681](index=681&type=chunk)[684](index=684&type=chunk) - **Relationships with customers and third-party payors are subject to anti-kickback, fraud and abuse, and other healthcare laws, exposing the company to criminal sanctions, civil penalties, and reputational harm**[504](index=504&type=chunk)[505](index=505&type=chunk)[506](index=506&type=chunk)[656](index=656&type=chunk)[685](index=685&type=chunk) - **Failure to comply with reporting and payment obligations under government pricing programs, such as Medicaid Drug Rebate, 340B, and VA FSS, could lead to penalties, sanctions, and fines**[689](index=689&type=chunk)[690](index=690&type=chunk)[692](index=692&type=chunk)[116](index=116&type=chunk) - **Penetrating foreign markets subjects the company to additional regulatory burdens, risks from political and economic instability, trade restrictions, and foreign currency fluctuations**[665](index=665&type=chunk)[666](index=666&type=chunk)[719](index=719&type=chunk)[861](index=861&type=chunk) - **Failure to comply with environmental, health, and safety laws could result in fines, penalties, or costs, materially affecting business success**[696](index=696&type=chunk)[721](index=721&type=chunk) [Risks Related to Our Dependence on Third Parties](index=130&type=section&id=Risks%20Related%20to%20Our%20Dependence%20on%20Third%20Parties) The company's reliance on third-party collaborations, CROs, and single-source manufacturers for drug development and supply poses significant risks, including potential termination of agreements, non-compliance, delays, and supply chain disruptions - **Collaborations and licenses with partners for drug development and commercialization may not be successful, leading to inability to capitalize on market potential or financial harm if agreements are terminated**[14](index=14&type=chunk)[735](index=735&type=chunk)[737](index=737&type=chunk)[762](index=762&type=chunk) - **Reliance on third-party Contract Research Organizations (CROs) for clinical trials means less direct control over development programs, with risks of non-compliance, delays, or termination if CROs fail to perform**[39](index=39&type=chunk)[738](index=738&type=chunk)[739](index=739&type=chunk)[765](index=765&type=chunk)[766](index=766&type=chunk)[770](index=770&type=chunk) - **Dependence on single-source third-party manufacturers for drugs and drug candidates increases the risk of insufficient quantities, delays, or impaired development and commercialization efforts**[27](index=27&type=chunk)[46](index=46&type=chunk)[47](index=47&type=chunk)[466](index=466&type=chunk)[741](index=741&type=chunk)[747](index=747&type=chunk)[771](index=771&type=chunk)[809](index=809&type=chunk) - **Manufacturing and supply activities in China through third parties expose the company to risks from natural disasters, epidemics, trade wars, political unrest, and currency fluctuations**[748](index=748&type=chunk)[810](index=810&type=chunk)[811](index=811&type=chunk) [Risks Related to Intellectual Property](index=140&type=section&id=Risks%20Related%20to%20Intellectual%20Property) The company's patent position is highly uncertain and subject to litigation, with risks of infringement allegations, expensive enforcement, and potential loss of exclusivity or trade secret confidentiality - **The patent position of biotechnology companies is highly uncertain and subject to litigation, with risks that patent protection may be unavailable, limited, or challenged**[40](index=40&type=chunk)[49](index=49&type=chunk)[750](index=750&type=chunk)[780](index=780&type=chunk)[812](index=812&type=chunk) - **Third parties may allege infringement of their intellectual property rights, leading to legal proceedings, uncertain outcomes, and potential material adverse effects on business success**[15](index=15&type=chunk)[54](index=54&type=chunk)[783](index=783&type=chunk)[815](index=815&type=chunk)[816](index=816&type=chunk) - **Litigation to protect or enforce patents is expensive, time-consuming, and may be unsuccessful, diverting resources and potentially leading to invalidation or narrow interpretation of patents**[55](index=55&type=chunk)[195](index=195&type=chunk)[196](index=196&type=chunk)[197](index=197&type=chunk)[751](index=751&type=chunk)[784](index=784&type=chunk)[817](index=817&type=chunk) - **Failure to obtain or maintain patent term extension or non-patent exclusivity, such as under the Hatch-Waxman Act, could shorten marketing exclusivity and reduce revenues**[198](index=198&type=chunk)[199](index=199&type=chunk)[200](index=200&type=chunk) - **Changes to patent law in the U.S. and other jurisdictions could diminish patent value, impairing the ability to protect drugs and drug candidates**[162](index=162&type=chunk)[163](index=163&type=chunk)[164](index=164&type=chunk) - **Inability to protect trade secret confidentiality could harm business and competitive position, as trade secrets may become known or independently discovered by competitors**[166](index=166&type=chunk)[167](index=167&type=chunk)[168](index=168&type=chunk) [Risks Related to Our Business, including Employee Matters, Managing Growth and Others](index=152&type=section&id=Risks%20Related%20to%20Our%20Business%2C%20including%20Employee%20Matters%2C%20Managing%20Growth%20and%20Others) The company's future success depends on retaining key personnel and managing growth, while facing risks from global economic conditions, foreign currency fluctuations, natural disasters, and cybersecurity breaches - **Future success depends on retaining key executives and attracting and retaining qualified personnel, with loss of key employees potentially impeding research and development and commercialization objectives**[131](index=131&type=chunk)[134](index=134&type=chunk)[135](index=135&type=chunk) - **The company expects to grow and expand operations, which may lead to difficulties in management, operational mistakes, loss of business opportunities, and increased expenses**[136](index=136&type=chunk)[137](index=137&type=chunk) - **Unfavorable global economic or political conditions, such as geopolitical conflicts and inflation, could adversely affect business, financial condition, and results of operations**[138](index=138&type=chunk)[140](index=140&type=chunk)[141](index=141&type=chunk)[142](index=142&type=chunk)[143](index=143&type=chunk)[229](index=229&type=chunk) - **Foreign currency exchange rate fluctuations could impact operating results, with U.S. dollar weakening increasing revenues but also expenses, and vice versa**[182](index=182&type=chunk) - **Natural disasters or other disruptions could severely disrupt operations, and existing business continuity plans may be inadequate**[183](index=183&type=chunk)[184](index=184&type=chunk) - **Internal computer systems or those of third parties may suffer security breaches, leading to disruption of development programs, reputational harm, and financial and legal liabilities**[186](index=186&type=chunk)[187](index=187&type=chunk)[188](index=188&type=chunk)[189](index=189&type=chunk)[190](index=190&type=chunk)[191](index=191&type=chunk)[193](index=193&type=chunk) [Risks Related to Our Financial Position and Need for Additional Capital](index=124&type=section&id=Risks%20Related%20to%20Our%20Financial%20Position%20and%20Need%20for%20Additional%20Capital) The company has incurred significant operating losses and expects continued losses, with substantial future capital requirements dependent on successful R&D and commercialization - **The company has incurred significant operating losses since inception, with a net loss of $507.0 million in 2023 and an accumulated deficit of $2,339.9 million, expecting continued losses**[26](index=26&type=chunk)[130](index=130&type=chunk)[700](index=700&type=chunk)[701](index=701&type=chunk)[724](index=724&type=chunk) - **Ability to generate substantial revenue and achieve profitability depends on successful clinical trials, regulatory approvals, commercialization, and market acceptance**[701](index=701&type=chunk)[702](index=702&type=chunk)[704](index=704&type=chunk)[725](index=725&type=chunk)[727](index=727&type=chunk) - **Future capital requirements are substantial and depend on research and development, commercialization, and collaboration activities, with an inability to raise funds on time or on attractive terms potentially forcing delays or discontinuation of programs**[705](index=705&type=chunk)[706](index=706&type=chunk)[708](index=708&type=chunk)[709](index=709&type=chunk)[728](index=728&type=chunk)[729](index=729&type=chunk)[730](index=730&type=chunk)[731](index=731&type=chunk) - **Raising additional capital through equity or debt could dilute stockholders, impose restrictive covenants, or require relinquishing valuable rights to intellectual property or drug candidates**[108](index=108&type=chunk)[731](index=731&type=chunk)[757](index=757&type=chunk)[759](index=759&type=chunk)[1103](index=1103&type=chunk) - **The company's substantial debt of $238.8 million net carrying value as of December 31, 2023, and the terms of the Financing Agreement with Sixth Street Partners could adversely affect operations and limit flexibility**[712](index=712&type=chunk)[733](index=733&type=chunk)[734](index=734&type=chunk)[760](index=760&type=chunk) [Risks Related to Our Common Stock](index=166&type=section&id=Risks%20Related%20to%20Our%20Common%20Stock) The price of common stock has been and may remain volatile, influenced by clinical trial results, competitive drugs, financial results, regulatory developments, and general market conditions - **The price of common stock has been and may remain volatile, influenced by clinical trial results, competitive drugs, financial results, regulatory developments, and general market conditions**[41](index=41&type=chunk)[76](index=76&type=chunk)[107](index=107&type=chunk)[166](index=166&type=chunk)[168](index=168&type=chunk)[806](index=806&type=chunk)[807](index=807&type=chunk)[808](index=808&type=chunk)[840](index=840&type=chunk) - **Future sales or issuances of common stock or other equity-related securities could lead to additional dilution for stockholders and adversely impact stock price**[107](index=107&type=chunk)[113](index=113&type=chunk)[778](index=778&type=chunk)[846](index=846&type=chunk) - **Negative evaluations or downgrades by equity research analysts could cause the common stock price to decline**[79](index=79&type=chunk)[842](index=842&type=chunk) - **Executive officers, directors, and principal stockholders hold significant influence over the company, potentially delaying or preventing acquisitions**[109](index=109&type=chunk)[870](index=870&type=chunk) - **Anti-takeover provisions in charter documents and Delaware law could make acquisitions more difficult and prevent changes in management**[80](index=80&type=chunk)[81](index=81&type=chunk)[111](index=111&type=chunk)[844](index=844&type=chunk) - **Exclusive forum provisions in bylaws may limit stockholders' ability to bring claims in preferred judicial forums, potentially discouraging lawsuits**[82](index=82&type=chunk)[112](index=112&type=chunk)[845](index=845&type=chunk)[872](index=872&type=chunk) - **Operating as a public company incurs substantial legal, accounting, and compliance costs, requiring significant management time**[84](index=84&type=chunk)[114](index=114&type=chunk)[847](index=847&type=chunk)[874](index=874&type=chunk) - **The company does not anticipate paying cash dividends, making capital appreciation the sole source of gain for stockholders**[85](index=85&type=chunk)[150](index=150&type=chunk)[856](index=856&type=chunk)[875](index=875&type=chunk) - **The ability to utilize net operating loss carryforwards and other tax attributes may be limited by ownership changes or tax law provisions, such as Tax Cuts and Jobs Act (TCJA) Section 382**[87](index=87&type=chunk)[105](index=105&type=chunk)[116](index=116&type=chunk)[849](index=849&type=chunk)[877](index=877&type=chunk)[1514](index=1514&type=chunk)[1515](index=1515&type=chunk) - **Stock repurchases may be subject to a new 1% excise tax, making them less desirable**[86](index=86&type=chunk)[876](index=876&type=chunk) [Unresolved Staff Comments](index=176&type=section&id=Item%201B.%20Unresolved%20Staff%20Comments.) The company has no unresolved staff comments from the SEC - **The company has no unresolved staff comments**[117](index=117&type=chunk) [Cybersecurity](index=176&type=section&id=Item%201C.%20Cybersecurity) This section details the company's cybersecurity governance, risk management, and strategy, overseen by the audit committee and managed by an information security team - **Cybersecurity is a board-level risk oversight, with the audit committee responsible for overseeing policies, practices, and assessments**[88](index=88&type=chunk)[851](index=851&type=chunk) - **The information security team, led by the Senior Vice President of Information Security (reporting to the CFO), manages cybersecurity risks based on the NIST Cybersecurity Framework, including security testing and monitoring**[119](index=119&type=chunk)[852](index=852&type=chunk) - **Processes include vendor risk assessment, security updates, penetration testing, and maintaining off-site backups and disaster recovery plans**[120](index=120&type=chunk) [Governance Related to Cybersecurity Risks](index=176&type=section&id=Governance%20Related%20to%20Cybersecurity%20Risks) The audit committee receives periodic updates on cybersecurity risks from the information security team, including biannual presentations on the risk management program status - **The audit committee receives periodic

AYVAKIT Performance - AYVAKIT's Q3 2023 revenue increased by 90% year-over-year[11, 13] - Approximately 800 patients were on AYVAKIT therapy in Q3 2023[11, 32] - 95% of U S lives are now covered for AYVAKIT's broad ISM label[25, 26] - The average time to fill AYVAKIT prescriptions is approximately 10 days[28] - In Q3 2023, 70% of new SM patient starts were prescribed a 25mg dose of AYVAKIT[34, 40] Financial Overview - Total revenue for Q3 2023 was $56 6 million, compared to $65 9 million in Q3 2022[43] - Net product sales for Q3 2023 were $54 2 million, a significant increase from $28 6 million in Q3 2022[43] - Research & Development expenses for Q3 2023 were $110 3 million[43] - The company had $827 2 million in cash, cash equivalents, and investments as of September 30, 2023[43] Strategic Focus - The company aims to penetrate a broader range of ISM patients, increase market growth through increased diagnosis, and expand geographically beyond the U S [37]

Financial Data and Key Metrics Changes - The company reported total revenues of $56.6 million for Q3 2023, including $54.2 million in net product revenues from AYVAKIT, marking a 90% growth compared to the previous year [24][40][31] - The number of patients on AYVAKIT therapy in the US increased to approximately 800, a significant rise of over 200 patients since the last quarter [10][24][75] Business Line Data and Key Metrics Changes - AYVAKIT's net product revenues nearly doubled from the same time last year, reflecting strong demand and effective market penetration [31][40] - The breadth of prescribing has expanded rapidly across various specialties, with allergists accounting for a significant portion of new systemic mastocytosis (SM) starts in Q3 [12][31] Market Data and Key Metrics Changes - The company has seen a substantial increase in the diagnosed prevalence of systemic mastocytosis, with estimates rising from about 11,000 patients in 2019 to over 17,000 or 18,000 currently [70][72] - Approximately 95% of lives are now covered by payer policies for AYVAKIT, indicating strong market access [14][31] Company Strategy and Development Direction - The core strategy focuses on extending leadership in systemic mastocytosis and expanding into other mast cell disorders, leveraging scientific innovation and commercial execution [16][20] - The company aims to broaden the adoption of AYVAKIT among a wider range of patients and expand into additional geographies, including anticipated approval in the EU [33][104] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in achieving sustainable revenue growth and a path to profitability, with expectations of a significant decrease in cash burn in 2024 [29][62] - The company is committed to maintaining a strong balance sheet while managing expenses effectively as revenues ramp up [61][63] Other Important Information - The company plans to provide 2024 revenue guidance inclusive of AYVAKIT on the Q4 earnings call, indicating a strong trajectory for the product [41][98] - AYVAKIT is positioned as a cornerstone of the company's franchise, with ongoing efforts to enhance its market presence and patient access [9][37] Q&A Session Summary Question: What are the portfolio goals and strategy updates for 2024? - Management indicated a focus on leveraging expertise in KIT biology and building relationships in the allergy immunology space, with a commitment to high standards for investment in long-term value [45][46] Question: Are there any insights into the patient retention rate? - Management noted that it is still early to provide specific retention rates, but there is confidence in continued strong and steady growth [128][98] Question: How is the company addressing the increase in diagnosis rates? - The company has seen a significant increase in diagnosed patients, attributing this to both the development of AYVAKIT and ongoing commercialization efforts [70][72] Question: What are the expectations for elenestinib's development after ASH? - Management views ASH as a critical step in demonstrating elenestinib's safety and activity, with plans to develop a robust data set for this next-generation therapy [85][109] Question: How does the company view the competitive landscape for AYVAKIT? - The company acknowledges that AYVAKIT has set a high bar for any new therapy, emphasizing the need for new agents to demonstrate broad symptom impact and a favorable safety profile [106][58]

PART I – FINANCIAL INFORMATION [Item 1. Financial Statements (unaudited)](index=4&type=section&id=Item%201.%20Financial%20Statements%20(unaudited)) Unaudited Q3 2023 financials show decreased assets, increased liabilities, and a net loss, with significant cash used in operations Condensed Consolidated Balance Sheet Highlights (in thousands) | Account | Sep 30, 2023 | Dec 31, 2022 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $55,972 | $119,709 | | Marketable securities | $771,254 | $958,763 | | Total current assets | $808,172 | $1,046,651 | | Total assets | $1,105,299 | $1,349,902 | | **Liabilities & Equity** | | | | Total current liabilities | $197,384 | $183,234 | | Liabilities related to sale of future royalties | $440,147 | $430,330 | | Term loan | $238,378 | $139,083 | | Total liabilities | $902,688 | $835,225 | | Total stockholders' equity | $202,611 | $514,677 | Condensed Consolidated Statements of Operations Highlights (in thousands, except per share data) | Metric | Q3 2023 | Q3 2022 | 9 Months 2023 | 9 Months 2022 | | :--- | :--- | :--- | :--- | :--- | | Product revenue, net | $54,228 | $28,634 | $133,173 | $80,929 | | Total revenues | $56,566 | $65,977 | $177,423 | $165,255 | | Research and development | $110,252 | $127,981 | $330,184 | $359,579 | | Selling, general and administrative | $70,741 | $57,608 | $215,826 | $173,354 | | Net loss | $(133,713) | $(133,163) | $(396,068) | $(398,871) | | Net loss per share | $(2.20) | $(2.23) | $(6.55) | $(6.70) | Condensed Consolidated Statements of Cash Flows Highlights (in thousands) | Cash Flow Activity | 9 Months Ended Sep 30, 2023 | 9 Months Ended Sep 30, 2022 | | :--- | :--- | :--- | | Net cash used in operating activities | $(357,919) | $(380,872) | | Net cash provided by (used in) investing activities | $195,271 | $(96,258) | | Net cash provided by financing activities | $103,697 | $559,319 | [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=33&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses Q3 product revenue growth driven by AYVAKIT, offset by decreased collaboration revenue, while maintaining strong liquidity for future self-sustainability [Overview](index=33&type=section&id=Overview) - The company is a global precision therapy company focused on cancer and blood disorders, with two approved medicines: AYVAKIT®/AYVAKYT® (avapritinib) and GAVRETO® (pralsetinib)[373](index=373&type=chunk) - Key development programs are advancing for mast cell disorders (AYVAKIT, elenestinib, BLU-808), EGFR-mutant lung cancer (BLU-945, BLU-525, BLU-451), and CDK2-vulnerable cancers (BLU-222)[373](index=373&type=chunk)[398](index=398&type=chunk)[403](index=403&type=chunk) - In February 2023, Roche elected to terminate the GAVRETO (pralsetinib) collaboration agreement, effective February 2024, with Blueprint regaining global rights (ex-Greater China) and seeking a new partner[391](index=391&type=chunk)[412](index=412&type=chunk)[423](index=423&type=chunk) - The company has entered into multiple financing arrangements, including a Royalty Purchase Agreement with Royalty Pharma and a Future Revenue Purchase Agreement and a term loan facility with Sixth Street Partners, to strengthen its financial position[434](index=434&type=chunk)[435](index=435&type=chunk)[436](index=436&type=chunk) [Results of Operations](index=47&type=section&id=Results%20of%20Operations) Comparison of Three Months Ended September 30, 2023 and 2022 (in thousands) | Line Item | Q3 2023 | Q3 2022 | $ Change | % Change | | :--- | :--- | :--- | :--- | :--- | | **Total revenues** | **$56,566** | **$65,977** | **$(9,411)** | **(14)%** | | Product revenue, net | $54,228 | $28,634 | $25,594 | 89% | | Collaboration & license revenue | $2,338 | $37,343 | $(35,005) | (94)% | | **Total cost & operating expenses** | **$185,546** | **$190,254** | **$(4,708)** | **(2)%** | | R&D Expense | $110,252 | $127,981 | $(17,729) | (14)% | | SG&A Expense | $70,741 | $57,608 | $13,133 | 23% | | **Net loss** | **$(133,713)** | **$(133,163)** | **$(550)** | **(0)%** | Comparison of Nine Months Ended September 30, 2023 and 2022 (in thousands) | Line Item | 9 Months 2023 | 9 Months 2022 | $ Change | % Change | | :--- | :--- | :--- | :--- | :--- | | **Total revenues** | **$177,423** | **$165,255** | **$12,168** | **7%** | | Product revenue, net | $133,173 | $80,929 | $52,244 | 65% | | Collaboration & license revenue | $44,250 | $84,326 | $(40,076) | (48)% | | **Total cost & operating expenses** | **$558,591** | **$552,974** | **$5,617** | **1%** | | R&D Expense | $330,184 | $359,579 | $(29,395) | (8)% | | SG&A Expense | $215,826 | $173,354 | $42,472 | 25% | | **Net loss** | **$(396,068)** | **$(398,871)** | **$2,803** | **1%** | - The **89% increase in Q3 product revenue** was primarily driven by growth in the number of SM patients on AYVAKIT therapy, including from the recent label expansion for indolent SM[297](index=297&type=chunk) - The decrease in Q3 collaboration revenue was mainly due to lower manufacturing services for Roche and CStone, and the absence of revenue from the Roche immunotherapy collaboration which terminated in April 2023[299](index=299&type=chunk)[300](index=300&type=chunk) - Q3 R&D expenses decreased by **14% YoY**, primarily due to a **$18.7 million reduction** in clinical and manufacturing activities reflecting a focused approach to optimizing operational efficiency[340](index=340&type=chunk) - Q3 SG&A expenses increased by **23% YoY**, driven by an **$8.0 million increase** in compensation for an expanded field team and a **$5.4 million increase** in commercial activities to support the indolent SM launch[467](index=467&type=chunk) [Liquidity and Capital Resources](index=55&type=section&id=Liquidity%20and%20Capital%20Resources) - As of September 30, 2023, the company had **$827.2 million** in cash, cash equivalents, and marketable securities[29](index=29&type=chunk)[497](index=497&type=chunk) - Management anticipates that existing cash, along with future product revenues, will be sufficient to achieve a self-sustainable financial profile[29](index=29&type=chunk) - In August 2023, the company drew down an additional **$100.0 million** in gross proceeds from its senior secured delayed draw term loan facility with Sixth Street Partners[95](index=95&type=chunk)[457](index=457&type=chunk) Cash Flow Summary (in thousands) | Cash Flow Activity | 9 Months Ended Sep 30, 2023 | 9 Months Ended Sep 30, 2022 | | :--- | :--- | :--- | | Net cash used in operating activities | $(357,919) | $(380,872) | | Net cash provided by (used in) investing activities | $195,271 | $(96,258) | | Net cash provided by financing activities | $103,697 | $559,319 | [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=58&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company's primary market risk is interest rate sensitivity on its $827.2 million investment portfolio, with limited exposure to foreign currency and inflation impacts - The primary market risk is interest rate sensitivity on the company's investment portfolio of **$827.2 million**, but a **10% change in rates** is not expected to have a material effect due to the short-term and low-risk nature of the investments[38](index=38&type=chunk)[39](index=39&type=chunk) - The company has limited exposure to foreign currency exchange rate risk from contracts with vendors in Asia and Europe and does not currently hedge this risk[41](index=41&type=chunk) - Inflation has not had a significant impact on the business to date, but sustained high inflation could increase costs for labor, clinical trials, and manufacturing[42](index=42&type=chunk) [Item 4. Controls and Procedures](index=59&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that disclosure controls and procedures were effective as of September 30, 2023, with no material changes to internal control over financial reporting - Management, including the CEO and CFO, concluded that as of September 30, 2023, the company's disclosure controls and procedures were effective at the reasonable assurance level[44](index=44&type=chunk) - No changes occurred during the fiscal quarter that materially affected, or are reasonably likely to materially affect, the company's internal control over financial reporting[45](index=45&type=chunk) PART II – OTHER INFORMATION [Item 1. Legal Proceedings](index=59&type=section&id=Item%201.%20Legal%20Proceedings) As of the reporting date, the company is not a party to any material legal proceedings - The company is not currently a party to any material legal proceedings[47](index=47&type=chunk) [Item 1A. Risk Factors](index=59&type=section&id=Item%201A.%20Risk%20Factors) The company faces significant risks including commercialization challenges, drug development and regulatory hurdles, reliance on third parties, financial sustainability, and intellectual property protection - **Commercialization Risks:** The marketing and sale of AYVAKIT and GAVRETO may be unsuccessful due to challenges in market acceptance by physicians and payors, substantial competition from other therapies, and the risk that market opportunities are smaller than estimated[53](index=53&type=chunk)[54](index=54&type=chunk)[112](index=112&type=chunk) - **Development & Regulatory Risks:** The company may be unable to obtain regulatory approval for drug candidates or for expanded indications (e.g., avapritinib for indolent SM outside the U.S.), experience delays in clinical trial enrollment, or encounter undesirable side effects that could halt development[55](index=55&type=chunk)[56](index=56&type=chunk)[194](index=194&type=chunk) - **Third-Party Reliance Risks:** The business depends on collaborations (e.g., the recently terminated Roche partnership for GAVRETO), third-party CROs to conduct clinical trials, and single-source third-party manufacturers for drug supply, which increases operational risk[60](index=60&type=chunk)[107](index=107&type=chunk)[108](index=108&type=chunk) - **Financial Risks:** The company has a history of operating losses and anticipates continued losses, with significant future capital requirements where an inability to raise additional funds could force delays or elimination of R&D programs or commercialization efforts[106](index=106&type=chunk)[519](index=519&type=chunk)[794](index=794&type=chunk) - **Intellectual Property Risks:** The company's ability to successfully commercialize its products may be impaired if it is unable to obtain and maintain sufficient patent protection or if it faces infringement lawsuits from competitors[61](index=61&type=chunk)[109](index=109&type=chunk) [Item 5. Other Information](index=112&type=section&id=Item%205.%20Other%20Information) During the third quarter of 2023, Ariel Hurley, the company's Senior Vice President of Finance and Principal Accounting Officer, adopted a Rule 10b5-1 trading plan for the sale of up to 16,867 shares of common stock - On September 13, 2023, an officer of the company adopted a Rule 10b5-1 trading arrangement for the potential sale of **16,867 shares of common stock**, effective through September 23, 2024[767](index=767&type=chunk)[768](index=768&type=chunk) [Item 6. Exhibits](index=112&type=section&id=Item%206.%20Exhibits) This section lists the exhibits filed with the Form 10-Q, including officer certifications pursuant to the Sarbanes-Oxley Act of 2002 and Inline XBRL documents - The report includes required certifications from the Principal Executive Officer and Principal Financial Officer (Exhibits 31.1, 31.2, 32.1) and Inline XBRL data files[769](index=769&type=chunk)

9 Second Quarter 2023 Financial Results AUGUST 2, 2023 INTRODUCTION AYVAKIT PERFORMANCE KEY PORTFOLIO MILESTONES Q2 2023 FINANCIAL PERFORMANCE Not for promotional use 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 Blueprint Medicines' current or future approved drugs and drug candi dates ...