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 ...

Blueprint Medicines Corporation (NASDAQ:BPMC) Q2 2023 Earnings Conference Call August 2, 2023 8:00 AM ET Company Participants Jenna Cohen - VP, IR Kate Haviland - CEO Philina Lee - CCO Fouad Namouni - President, R&D Mike Landsittel - CFO Christy Rossi - COO Becker Hewes - CMO Conference Call Participants Brad Canino - Stifel Dane Leone - Raymond James Reni Benjamin - JMP Securities Eun Yang - Jefferies Marc Frahm - TD Cowen Salveen Richter - Goldman Sachs Michael Schmidt - Guggenheim Partners Ami Fadia - Ne ...

Table of Contents The Company evaluated the Zai Lab agreement to determine whether it is a collaborative arrangement in the scope of ASC 808. The Company concluded that the Zai Lab agreement is a collaborative agreement under ASC 808 as both parties are active participants in the clinical trials and are exposed to significant risks and rewards of those activities under the Zai Lab agreement. The Company determined that the Zai Lab agreement contained two material components: (i) licenses granted to Zai Lab ...

Blueprint Medicines Corporation (NASDAQ:BPMC) Q1 2023 Earnings Conference Call May 4, 2023 8:00 AM ET Company Participants Jenna Cohen - Senior Director and Head, Investor Relations Kate Haviland - Chief Executive Officer Philina Lee - Chief Commercial Officer Becker Hewes - Chief Medical Officer Mike Landsittel - Chief Financial Officer Fouad Namouni - President, Research & Development Christina Rossi - Chief Operating Officer Conference Call Participants Reni Benjamin - JMP Securities Brad Canino - Stifel ...

4. Marketable Securities | --- | --- | --- | --- | --- | --- | --- | --- | |------------------------------------------------|-------|--------------------|-------------------|-------|-----------------------|-------|--------------| | thousands): \nMarch 31, 2023 | | Amortized \nCost | Unrealized \nGain | | Unrealized \nLosses | | Fair \nValue | | Marketable securities, available-for-sale: | | | | | | | | | U.S. government agency securities | $ | 314,891 | | 28 | (2,117) | $ | 312,802 | | U.S. treasury obligat ...

Financial Data and Key Metrics Changes - For the full year 2022, total revenues were $204 million, including $111 million in net product revenues from AYVAKIT and $93 million in collaborations and license revenues, exceeding the high end of the 2022 total revenue guidance of $200 million [46][73] - Total operating expenses were $723.7 million for the full year, with Q4 operating expenses showing a quarter-over-quarter decline from Q3 as the company continues to leverage operating efficiencies [47][48] - The company expects operating expenses to grow moderately in Q1 2023, driven by preparations for the ISM launch and planned manufacturing investments [48] Business Line Data and Key Metrics Changes - AYVAKIT net product revenue doubled year-over-year in 2022, achieving $111 million, with Q4 revenues at $30.1 million, of which $26.3 million came from the U.S. [18][46] - The company anticipates AYVAKIT net product revenues of $130 million to $140 million in 2023, representing a more than 20% increase year-over-year [20][73] Market Data and Key Metrics Changes - The U.S. accounted for the majority of AYVAKIT product sales, with nearly 500 patients on AYVAKIT by the end of 2022 [8][34] - The company is preparing for the ISM launch, targeting approximately 7,500 patients with moderate to severe ISM, who are actively seeking treatment [36][40] Company Strategy and Development Direction - The company aims to expand its leadership in systemic mastocytosis and advance its clinical stage pipeline focused on best-in-class investigational therapies [13][31] - The strategy includes engaging a broader provider base for ISM patients and maintaining strong patient access to therapy [22][40] - The company is focused on achieving a sustainable financial profile while executing on a range of opportunities [31] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the growth trajectory for AYVAKIT and the anticipated launch in ISM, highlighting the strong medical need and motivated patient base [40][128] - The company is optimistic about capturing the significant ISM opportunity, supported by a strong cash position of over $1 billion [15][74] Other Important Information - The company has received EMA validation for its type 2 variation for AYVAKIT and ISM, bringing it closer to the important indication expansion and launch in Europe [69] - The FDA issued a partial clinical hold on the VELA trial due to visual adverse events, but the company is working closely with the FDA to resolve this issue [45][120] Q&A Session Summary Question: What is the overlap between current prescriber base of AYVAKIT and potential ISM patients? - The company indicated that among the top 350 prescribers, there are nearly 400 moderate to severe ISM patients who could rapidly start AYVAKIT upon approval [76][88] Question: What is the current thinking regarding vision events and the CDK2 program? - Management stated that the FDA is working cooperatively to modify the protocol and informed consent regarding the vision events observed [56][120] Question: How does the company view the early trajectory for ISM? - The company does not anticipate an initial launch bolus but expects gradual growth driven by increased disease awareness and advanced patient identification capabilities [126][128] Question: What is the current payer coverage for ISM? - The company reported strong payer coverage with virtually no access challenges for SM patients, and they do not expect a new code for ISM [153][183] Question: How is the sales force adapting to focus on allergists? - The company has expanded its field force to engage a broader provider base, including allergists, and has achieved over 40% awareness of AYVAKIT among target prescribers [149][150]

Brexit and the Regulatory Framework in the United Kingdom The UK formally left the EU on January 31, 2020, and the EU and the UK have concluded a trade and cooperation agreement, or TCA, which was provisionally applicable since January 1, 2021 and has been formally applicable since May 1, 2021. The TCA includes specific provisions concerning pharmaceuticals, which include the mutual recognition of GMP, inspections of manufacturing facilities for medicinal products and GMP documents issued, but does not fore ...