Elenestinib

-- Achieved $114.1 million in AYVAKIT net product revenues in the second quarter 2024 -- -- Raising AYVAKIT net product revenue guidance to $435 million to $450 million for 2024 -- -- Initiated Phase 1 healthy volunteer trial of wild-type KIT inhibitor BLU-808 -- CAMBRIDGE, Mass., Aug. 1, 2024 /PRNewswire/ -- Blueprint Medicines Corporation (Nasdaq: BPMC) today reported financial results, provided a business update for the second quarter ended June 30, 2024, and provided updated financial guidance. "This quarter marks a milestone, as we celebrate one full year since the U.S. approval of AYVAKIT for indolent systemic mastocytosis. We have delivered yet another very strong quarter of revenue as we continue to build this new rare disease market, and we are well on the path to achieve more than $2 billion in potential peak sales. In addition, we have invested in our next pillars of growth, building on AYVAKIT as the cornerstone of a mast cell disease franchise. Our wild-type KIT inhibitor BLU-808 has entered a Phase 1 healthy volunteer study and we expect to initiate the registration-enabling HARBOR Part 2 study of our next-generation KIT D816V inhibitor elenestinib in indolent systemic mastocytosis later this year," said Kate Haviland, Chief Executive Officer of Blueprint Medicines. "With a significant and growing revenue base from AYVAKIT, a next wave of therapies in our pipeline that we believe can address even larger scale patient opportunities, and a financial profile anchored in sustainable topline revenue growth that enables us the flexibility to invest in the next wave of innovation, we are building Blueprint Medicines for long term value." Second Quarter 2024 Highlights and Recent Progress Mast cell disorders Achieved AYVAKIT net product revenues of $114.1 million for second quarter of 2024, representing more than 185 percent growth year-over-year. Achieved clearance of an Investigational New Drug application for BLU-808 by the U.S. Food and Drug Administration and initiated the healthy volunteer study. BLU-808 is a highly selective and potent investigational oral wild-type KIT inhibitor with best-in-class potential, for chronic urticaria and other mast cell disorders. Presented multiple datasets highlighting the long-term safety and durable clinical outcomes of AYVAKIT®/AYVAKYT® (avapritinib) across the spectrum of systemic mastocytosis (SM) at the 2024 European Academy of Allergy and Clinical Immunology (EAACI) and European Hematology Association (EHA) conferences. Read the presentations here. Cell cycle inhibition Presented data from the Phase 1 VELA study of BLU-222, an oral, potent and selective CDK2 inhibitor, at the 2024 American Society of Clinical Oncology (ASCO) meeting. This is the first positive combination safety data with signals of early clinical activity for a CDK2 inhibitor in combination with an approved CDK4/6 inhibitor, ribociclib, and fulvestrant, in patients with HR+/HER2- breast cancer. Read the presentation here. 2024 Financial Guidance Blueprint Medicines now anticipates approximately $435 million to $450 million in global AYVAKIT net product revenues for all approved indications in 2024, an increase from the previous range of $390 million to $410 million. The company continues to expect that full-year operating expenses and cash burn will decline in 2024 as compared to 2023, and that its existing cash, cash equivalents and investments, together with anticipated product revenues, will enable the company to maintain a durable capital position to achieve a self-sustainable financial profile. Key Upcoming Milestones The company plans to achieve the following remaining milestones in the second half of 2024: Mast cell disorders Initiate registration-enabling Part 2 of the HARBOR trial in indolent systemic mastocytosis (ISM). Cell cycle inhibition Continue strategic business development discussions. Complete Phase 1 combination dose escalation for BLU-222 by end of year to inform registration plans. Second Quarter 2024 Results Revenues: Revenues were $138.2 million for the second quarter of 2024, including $114.1 million of net product revenues from sales of AYVAKIT/AYVAKYT and $24.0 million in collaboration, license and other revenues. Revenues were $57.6 million in the second quarter of 2023, including $39.9 million of net product revenues from sales of AYVAKIT/AYVAKYT and $17.7 million in collaboration, license and other revenues. Cost of Sales: Cost of sales was $7.6 million for the second quarter of 2024, as compared to $2.3 million for the second quarter of 2023. The increase was primarily due to the sale of GAVRETO® (pralsetinib) product to Rigel. R&D Expenses: Research and development expenses were $84.3 million for the second quarter of 2024, as compared to $110.1 million for the second quarter of 2023. This decrease was primarily due to operational efficiency across our portfolio as we execute across our top priority programs and the timing of manufacturing of clinical trial materials. Research and development expenses included $12.3 million in stock-based compensation expenses for the second quarter of 2024. SG&A Expenses: Selling, general and administrative expenses were $89.3 million for the second quarter of 2024, as compared to $71.9 million for the second quarter of 2023. This increase was primarily due to an increase in activities supporting the commercialization of AYVAKIT/AYVAKYT. Selling, general, and administrative expenses included $15.7 million in stock-based compensation expenses for the second quarter of 2024. Net Loss: Net loss was $50.0 million for the second quarter of 2024, as compared to a net loss of $132.8 million for the second quarter of 2023 . Cash Position: As of June 30, 2024, cash, cash equivalents and investments were $868.5 million, as compared to $767.2 million as of December 31, 2023. This increase was primarily due to taking an additional draw under our 2022 debt facility with Sixth Street Partners. Blueprint Medicine's cash and investments provide a durable capital position which, together with anticipated product revenues, the company believes will enable it to reach a self-sustainable financial profile . Conference Call Information Blueprint Medicines will host a live conference call and webcast at 8:00 a.m. ET today to discuss second quarter 2024 financial results and recent business activities. The conference call may be accessed by dialing 833-470-1428 (domestic) or 404-975-4839 (international), and referring to conference ID 299779. A webcast of the call will also be available under "Events and Presentations" in the Investors & Media section of the Blueprint Medicines website at . The archived webcast will be available on Blueprint Medicines' website approximately two hours after the conference call and will be available for 30 days following the call. Upcoming Investor Conferences Blueprint Medicines will participate in two upcoming investor conferences: Morgan Stanley 22nd Annual Global Healthcare Conference on Thursday, September 5, 2024 at 1:50 p.m. ET. 2024 Wells Fargo Healthcare Conference on Thursday, September 5, 2024 at 11:00 a.m. ET. A live webcast of the fireside discussions will be available under "Events and Presentations" in the Investors & Media section of the Blueprint Medicines website at . A replay of the webcasts will be archived on the Blueprint Medicines website for 30 days following the events. About Blueprint Medicines Blueprint Medicines is a global, fully integrated biopharmaceutical company that invents life-changing medicines. We seek to alleviate human suffering by solving important medical problems in two core focus areas: allergy/inflammation and oncology/hematology. Our approach begins by targeting the root causes of disease, using deep scientific knowledge in our core focus areas and drug discovery expertise across multiple therapeutic modalities. We have a track record of success with two approved medicines, including AYVAKIT®/AYVAKYT® (avapritinib) which we are bringing to patients with systemic mastocytosis (SM) in the U.S. and Europe. Leveraging our established research, development, and commercial capability and infrastructure, we now aim to significantly scale our impact by advancing a broad pipeline of programs ranging from early science to advanced clinical trials in mast cell diseases including SM and chronic urticaria, breast cancer and other solid tumors. For more information, visit and follow us on X (formerly Twitter; @BlueprintMeds) and LinkedIn. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding plans, strategies, timelines and expectations for Blueprint Medicines' operations, including its expectations regarding growth and product revenue in 2024; statements regarding our current or future approved drugs and drug candidates and operations, including AYVAKIT's potential to achieve more than $2 billion in peak sales; plans to initiate registration-enabling Part 2 of the HARBOR trial in ISM, complete Phase 1 combination dose escalation for BLU-222 to inform registration plans and continue strategic business development discussions all in the second half of 2024; plans to advance our portfolio by targeting additional allergic-inflammatory diseases driven by mast cells; expectations related to the markets for our current or future approved drugs and drug candidates, including expectations regarding the size or scale of patient opportunities that our future approved drugs and drug candidates could address; the potential benefits of any of our current or future approved drugs or drug candidates in treating patients; statements related to our liquidity and capital position, including expectations that our cash, cash equivalents and investments will provide a durable capital position which, together with anticipated product revenues, will enable us to reach a self-sustainable financial profile; and our financial performance, strategy, goals and anticipated milestones, business plans and focus, including expectations regarding our revenue ramp and continued decline in operating expenses and cash burn. The words "aim," "may," "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," "estimate," "predict," "project," "potential," "continue," "target" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation: the risk that the marketing and sale of AYVAKIT/ AYVAKYT or any future approved drugs may be unsuccessful or less successful than anticipated, or that AYVAKIT/ AYVAKYT may not gain market acceptance by physicians, patients, third-party payors and others in the medical community; the risk that the market opportunities for AYVAKIT/ AYVAKYT or our drug candidates are smaller than we estimate or that any approval we obtain may be based on a narrower definition of the patient population that we anticipate; the risk of delay of any current or planned clinical trials or the development of Blueprint Medicines' current or future drug candidates; risks related to Blueprint Medicines' ability to successfully demonstrate the safety and efficacy of its drug candidates and gain approval of its drug candidates on a timely basis, if at all; preclinical and clinical results for Blueprint Medicines' drug candidates may not support further development of such drug candidates either as monotherapies or in combination with other agents or may impact the anticipated timing of data or regulatory submissions; the timing of the initiation of clinical trials and trial cohorts at clinical trial sites and patient enrollment rates may be delayed or slower than anticipated; actions of regulatory agencies may affect our approved drugs or our current or future drug candidates, including affecting the initiation, timing and progress of clinical trials; risks related to Blueprint Medicines' ability to obtain, maintain and enforce patent and other intellectual property protection for its products and current or future drug candidates it is developing; the success of Blueprint Medicines' current and future collaborations, financing arrangements, partnerships or licensing and other arrangements; risks related to our liquidity and financial position, including the risk that we may be unable to generate sufficient future product revenues to achieve and maintain a self-sustainable financial profile; and the accuracy of our estimates of revenues, expenses and capital requirements. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in Blueprint Medicines' filings with the Securities and Exchange Commission (SEC), including Blueprint Medicines' most recent Annual Report on Form 10-K, as supplemented by its most recent Quarterly Report on Form 10-Q and any other filings that Blueprint Medicines has made or may make with the SEC in the future. Any forward-looking statements contained in this press release represent Blueprint Medicines' views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, Blueprint Medicines explicitly disclaims any obligation to update any forward-looking statements. Trademarks Blueprint Medicines, AYVAKIT, AYVAKYT and associated logos are trademarks of Blueprint Medicines Corporation. GAVRETO and associated logos are trademarks of Blueprint Medicines Corporation outside of the United States. SOURCE Blueprint Medicines Corporation

01 c-Kit激酶 c-Kit激酶是人体中众多酪氨酸激酶中的一种，其本质是一种跨膜蛋白。c-Kit蛋白通过激活各种信号通路，对细胞的增值，分化，存活，以及迁移起着重要的作用。 c-Kit蛋白由胞外区，跨膜区和胞内区三部分组成。其中,胞外区由5个免疫球蛋白样结构域组成，跨膜区为一次跨膜α螺旋，胞内区为受体催化域，具体分为近膜（juxtamembrane (JM)域，酪氨酸激酶1域，酪氨酸激酶插入域，酪氨酸激酶2域。在正常的状态下，失活时c-Kit以单体形式存在；一旦与配体干细胞因子结合，c-Kit就会二聚化。二聚化的单体相互在Y568，Y570和（或）Y823发生自身磷酸化，从而激活下游信号通路，引起细胞生长和分化。一些含有SH2和蛋白酪氨酸结合域的蛋白，如蛋白酪氨酸磷酸酶 SHP-1，细胞因子抑制剂6（suppressor of cytokine signaling 6 ，SOCS6）等，是c-Kit活性的负调控蛋白。 已有研究表明，c-Kit的丧失功能突变会导致耳聋，便秘等疾病；而获得功能的突变则与胃肠基质瘤（GIST），肥大细胞白血病（MCL），急性髓系白血病（AML）等疾病有关。临床上针对酪氨酸激酶的小分子抑制剂用来治疗各种癌症，并且，对于不同的癌症病人都已经有了很多可选择的治疗方案，这些特异的对激酶信号通路的抑制能够导致肿瘤的生长大小，生长速度，延缓病情恶化。 02 c-Kit在研格局 根据新药情报库所披露信息 ，目前c-kit靶点共有在研药物112个，包含的适应症有557种，在研机构211家，涉及相关的临床试验4892件，专利多达21701件…… 多款特异性c-KIT抑制剂已进入临床研究阶段，如Bezuclastinib（PLX-9486）、KTN-0158、JSP-191、BLU-263、CDX-0159，等十几项临床研究在海外进行中，其中除Bezuclastinib、BLU-263 进展较快已进入Ⅲ期阶段外，大多为I期临床研究。 6月12日，Celldex Therapeutics在Clinicaltrials.gov网站上注册了Barzolvolimab治疗慢性自发性荨麻疹（CSU）的三期临床试验。Barzolvolimab为一款KIT抗体，是Celldex的首发管线，正在探索多种自免适应症，此前的二期临床在表现出优异的疗效。 国内来看，聚焦自免的荃信生物，今年2月申报了一款针对c-kit靶点的人源化IgG1单克隆抗体QX013N，今年5月获批临床，拟开发用于治疗慢性自发性荨麻疹（CSU）。 03 展望 过去十年，KIT抑制剂在GIST等肿瘤领域的应用为患者治疗带来新的选择和方向。然而,仍有相当部分患者初始治疗无效, 或出现继发耐药。临床实践中, 可以考虑与其它治疗策略进行联用, 包括化疗、放疗、各种分子靶向药物、免疫抑制剂、细胞因子抑制剂、病毒疗法及肿瘤疫苗等。相信随着恶性肿瘤的治疗及耐药机制探索的不断深入, 未来越来越多的患者将会从治疗中获益。 吉满生物特色产品 为满足c-Kit相关药物研发需求，吉满生物分别开发出高质量的稳定过表达细胞株和抗体，可用于抗体筛选、表征、一致性评价, 充分满足药物研发的需求，助力抗体药物临床申报。除此之外，吉满生物还可提供高活性c-Kit重组蛋白，可满足客户在动物免疫、抗体筛选以及表位鉴定等不同场景中的需求，所有产品均已通过严格的质量监测。(咨询吉满客服联系同微信:18916119826）。 产品列表 数据展示（部分）： GM-C36580 H_c-Kit(CD117) GNNK(-) CHO-K1 Cell Line使用Anti-c-Kit(CD117) hIgG1 Antibody(barzolvolimab)流式验证 GM-C36717 H_c-Kit(CD117) GNNK(+) CHO-K1 Cell Line使用Anti-c-Kit(CD117) hIgG1 Antibody(barzolvolimab)流式验证结果 GM-C36581 Cynomolgus_c-Kit(CD117) GNNK(-) CHO-K1 Cell Line使用Anti-c-Kit(CD117) hIgG1 Antibody(barzolvolimab)流式验证结果 蛋白数据展示 GM-87117RP   Human c-Kit(CD117) Protein His Tag SDS-PAGE On SDS-PAGE under reducing (R) condition. The gel was stained overnight with Coomassie Blue. The purity of the protein is greater than 95%. ★ His Tag ELISA验证  His Tag (Catalog # GM-87117RP) was immobilized at 2 μg/ml (100 μL/well). Increasing concentrations of Human SCF Protein; mFc Tag (Catalog # GM-87653RP) were added. ★  His Tag ELISA验证 His Tag (Catalog # GM-87117RP) was immobilized at 2 μg/ml (100 μL/well). Increasing concentrations of Anti-c-Kit(CD117) hIgG1 Antibody(barzolvolimab) (Catalog # GM-86542AB) were added. ★ GM-87120RP   Cynomolgus c-Kit(CD117) Protein  His Tag SDS-PAGE On SDS-PAGE under reducing (R) condition. The gel was stained overnight with Coomassie Blue. The purity of the protein is greater than 95%. ★ His Tag ELISA验证 Cynomolgus c-Kit(CD117) Protein; His Tag (Catalog # GM-87120RP) was immobilized at 2 μg/ml (100 μL/well). Increasing concentrations of Anti-c-Kit(CD117) hIgG1 Antibody(barzolvolimab) (Catalog # GM-86542AB) were added. ★ GM-87119RP   Human c-Kit(CD117) Protein hFc Tag SDS-PAGE On SDS-PAGE under nun-reducing (NR) condition and reducing (R) condition. The gel was stained overnight with Coomassie Blue. The purity of the protein is greater than 95%. ★  hFc Tag ELISA验证 Human SCF Protein; His Tag (Catalog # GM-87651RP) was immobilized at 2 μg/ml (100 μL/well). Increasing concentrations of Human c-Kit(CD117) Protein; hFc Tag (Catalog # GM-87119RP) were added. 联系我们 吉满生物助力药物研发，紧随前沿靶点资讯，储备几百株现货细胞，覆盖GPCR、细胞因子、免疫检查点、TAA等多领域，截止当前已布局近300个热门靶向药靶点，1000余株细胞系，旨在助力、加速大分子早期研发，做到进口细胞的国产替代。同时可根据客户需求提供细胞系服务。 扫码咨询 扫码找现货