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-- FDA grants priority review and sets PDUFA action date of May 22, 2023 -- CAMBRIDGE, Mass., Jan. 23, 2023 /PRNewswire/ -- Blueprint Medicines Corporation (NASDAQ: BPMC) today announced that the U.S. Food and Drug Administration (FDA) has accepted the company's supplemental new drug application for AYVAKIT® (avapritinib) for the treatment of adults with indolent systemic mastocytosis (SM). The FDA granted priority review with an action date of May 22, 2023 under the Prescription Drug User Fee Act (PDUFA). This regulatory application is based on results from the global PIONEER trial, the largest randomized, placebo-controlled study ever conducted in indolent SM. The FDA previously granted breakthrough therapy designation to AYVAKIT for the treatment of moderate to severe indolent SM. AYVAKIT was designed to potently and selectively inhibit D816V mutant KIT, the primary underlying cause of SM. "People with indolent systemic mastocytosis experience debilitating symptoms and poor quality of life, and we have the potential to transform clinical outcomes for these patients by targeting the genetic driver of disease with AYVAKIT," said Becker Hewes, M.D., Chief Medical Officer at Blueprint Medicines. "AYVAKIT achieved the primary and all key secondary endpoints in the PIONEER trial, with highly meaningful reductions in patient-reported symptoms and all measures of mast cell burden studied, and a well-tolerated safety profile supporting chronic treatment. We look forward to collaborating with the FDA during its review process, with the goal of bringing the first approved medicine to patients with indolent SM and redefining the treatment landscape beyond symptom-directed therapies." About AYVAKIT (avapritinib) AYVAKIT (avapritinib) is a kinase inhibitor approved by the FDA for the treatment of adults with Advanced SM, including aggressive SM (ASM), SM with an associated hematological neoplasm (SM-AHN) and mast cell leukemia (MCL), and adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. For more information, visit AYVAKIT.com. This medicine is approved in Europe (AYVAKYT®) for the treatment of adults with ASM, SM-AHN or MCL, after at least one systemic therapy, and adults with unresectable or metastatic GIST harboring the PDGFRA D842V mutation. Please click here to see the full U.S. Prescribing Information for AYVAKIT, and click here to see the European Summary of Product Characteristics for AYVAKYT. AYVAKIT/AYVAKYT is not approved for the treatment of any other indication in the U.S. or Europe. To learn about ongoing or planned clinical trials, contact Blueprint Medicines at [email protected] or 1-888-BLU-PRNT (1-888-258-7768). Additional information is available at blueprintclinicaltrials.com or clinicaltrials.gov. About Systemic Mastocytosis Systemic mastocytosis (SM) is a rare disease driven by the KIT D816V mutation in about 95 percent of cases. Uncontrolled proliferation and activation of mast cells result in chronic, severe and often unpredictable symptoms across multiple organ systems. Most of those affected have non-advanced (indolent or smoldering) SM, and among these patients, the vast majority have indolent SM. A broad range of symptoms, including anaphylaxis, maculopapular rash, pruritis, diarrhea, brain fog, fatigue and bone pain, frequently persist in patients with non-advanced SM despite treatment with multiple symptom-directed therapies. This burden of disease can lead to a profound, negative impact on quality of life. Patients often live in fear of severe, unexpected symptoms, have limited ability to work or perform daily activities, and isolate themselves to protect against unpredictable triggers. Currently, there are no approved therapies for the treatment of non-advanced SM. A minority of patients have advanced SM, which encompasses a group of high-risk SM subtypes including ASM, SM-AHN and MCL. In addition to mast cell activation symptoms, advanced SM is associated with organ damage due to mast cell infiltration and poor survival. About Blueprint Medicines Blueprint Medicines is a global precision therapy company that invents life-changing therapies for people with cancer and blood disorders. Applying an approach that is both precise and agile, we create medicines that selectively target genetic drivers, with the goal of staying one step ahead across stages of disease. Since 2011, we have leveraged our research platform, including expertise in molecular targeting and world-class drug design capabilities, to rapidly and reproducibly translate science into a broad pipeline of precision therapies. Today, we are delivering our approved medicines to patients in the United States and Europe, and we are globally advancing multiple programs for systemic mastocytosis, lung cancer, breast cancer and other genomically defined cancers, and cancer immunotherapy. For more information, visit and follow us on Twitter (@BlueprintMeds) and LinkedIn. Cautionary Note Regarding 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 interactions with the U.S. Food and Drug Administration (FDA) and other regulatory authorities; statements regarding the plans and potential benefits of AYVAKIT in treating patients with indolent SM; statements regarding plans and expectations for Blueprint Medicines' current or future approved drugs and drug candidates; the potential benefits of any of the company's current or future approved drugs or drug candidates in treating patients; and Blueprint Medicines' financial performance, strategy, goals and anticipated milestones, business plans and focus. The words "aim," "may," "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," "estimate," "predict," "project," "potential," "continue," "target" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks and uncertainties related to the impact of the COVID-19 pandemic to Blueprint Medicines' business, operations, strategy, goals and anticipated milestones, including Blueprint Medicines' ongoing and planned research and discovery activities, ability to conduct ongoing and planned clinical trials, clinical supply of current or future drug candidates, commercial supply of current or future approved products, and launching, marketing and selling current or future approved products; Blueprint Medicines' ability and plans in continuing to establish and expand a commercial infrastructure, and successfully launching, marketing and selling current or future approved products; Blueprint Medicines' ability to successfully expand the approved indications for AYVAKIT/AYVAKYT or obtain marketing approval for AYVAKIT/AYVAKYT in additional geographies in the future; the delay of any current or planned clinical trials or the development of Blueprint Medicines' current or future drug candidates; Blueprint Medicines' advancement of multiple early-stage efforts; Blueprint Medicines' ability to successfully demonstrate the safety and efficacy of its drug candidates and gain approval of its drug candidates on a timely basis, if at all; the preclinical and clinical results for Blueprint Medicines' drug candidates, which may not support further development of such drug candidates either as monotherapies or in combination with other agents or may impact the anticipated timing of data or regulatory submissions; the timing of the initiation of clinical trials and trial cohorts at clinical trial sites and patient enrollment rates; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials; Blueprint Medicines' ability to obtain, maintain and enforce patent and other intellectual property protection for AYVAKIT/AYVAKYT or any drug candidates it is developing; Blueprint Medicines' ability to develop and commercialize companion diagnostic tests for AYVAKIT/AYVAKYT or any of its current and future drug candidates; Blueprint Medicines' ability to successfully expand its operations, research platform and portfolio of therapeutic candidates, and the timing and costs thereof; and the success of Blueprint Medicines' current and future collaborations, financing arrangements, partnerships or licensing arrangements. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in Blueprint Medicines' filings with the Securities and Exchange Commission (SEC), including Blueprint Medicines' most recent Annual Report on Form 10-K, as supplemented by its most recent Quarterly Report on Form 10-Q and any other filings that Blueprint Medicines has made or may make with the SEC in the future. Any forward-looking statements contained in this press release represent Blueprint Medicines' views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, Blueprint Medicines explicitly disclaims any obligation to update any forward-looking statements. Trademarks Blueprint Medicines, AYVAKIT, AYVAKYT and associated logos are trademarks of Blueprint Medicines Corporation. SOURCE Blueprint Medicines Corporation

Courtesy of Shutterstock In June, Day One Biopharmaceutical's stock shot into the stratosphere after it announced positive early data from the Phase II Firefly-1 trial of tovorafenib in relapsed or progressive pediatric low-grade glioma. Monday, the company was back with topline data. In 69 evaluable patients, tovorafenib as a monotherapy elicited a 64% overall response rate and 91% clinical benefit rate (defined as complete response + partial response/unconfirmed partial response + stable disease). There were three confirmed complete responses and 41 partial responses (31 confirmed). Median treatment duration was 8.4 months. The ORR and clinical benefit rates were identical to those reported from 22 patients in June. Day One reported that tovorafenib was "generally well-tolerated," with the most common side effects being changes in hair color, increased creatine phosphokinase, anemia, fatigue and maculopapular rash. The company picked up a 20% stock bump for these largely confirmatory data. With these positive data in hand, the South San Francisco-based company intends to seek approval for the therapy in the first half of 2023. The New Drug Application "will include additional follow-up from the full study population," said CEO Jeremy Bender, Ph.D. in a prepared statement. Tovorafenib, an oral, type II Pan-RAF kinase inhibitor designed to target a key enzyme in the MAPK signaling pathway, is being developed to treat patients 6-to-25 years with recurrent or progressive pLGG. The MAPK pathway is one of cancer's most commonly mutated oncogenic pathways. pLGG is the most commonly diagnosed pediatric brain tumor for which there is no current standard of care. While highly survivable, children often endure multiple lines of therapy, significantly impacting their quality of life. Despite the Pediatric Research Equity Act, passed in the U.S. in 2003, clinical trials for pediatric cancers still pale in comparison to those for adult diseases. This is where Day One's unique business model comes into play. The company leverages the return on investment from an "all-patients" approach to intentionally develop effective cancer therapies for kids. The intent, Bender told BioSpace in a previous interview, is "to bridge the gap between pediatric and adult patients in terms of therapeutic options." Tovorafenib is also being developed as a front-line therapy for plGG in the Phase III Firefly-2 trial and for adolescents and adults with recurrent or progressive solid tumors with aberrations in the MAPK pathway. Featured Jobs on BioSpace

Overall response rate (ORR) of 64% and clinical benefit rate (CBR) of 91% in 69 heavily-pretreated, RANO-evaluable patientsMedian duration of 8.4 months on therapy as of September 28, 2022, with 77% of patients remaining on treatmentAdditional data to be presented at a medical meeting in the second quarter of 2023New Drug Application submission planned for first half of 2023 SOUTH SAN FRANCISCO, Calif., Jan. 08, 2023 (GLOBE NEWSWIRE) -- Day One Biopharmaceuticals (Nasdaq: DAWN), a clinical-stage biopharmaceutical company dedicated to developing and commercializing targeted therapies for people of all ages with life-threatening diseases, today announced positive topline results from the ongoing, open-label, pivotal Phase 2 FIREFLY-1 trial evaluating the investigational agent, tovorafenib (DAY101), as a monotherapy in recurrent or progressive pediatric low-grade glioma (pLGG). Pediatric low-grade glioma is the most common brain tumor diagnosed in children and for which there is no standard of care, and for which there are no approved therapies for the majority of patients. Additional data will be submitted for presentation at an upcoming medical meeting in the second quarter of 2023. The primary endpoint of the FIREFLY-1 trial is overall response rate (ORR) by Response Assessment for Neuro-Oncology (RANO) criteria as assessed by blinded independent central review. Topline results as of September 28, 2022 include: Among 69 RANO-evaluable patients: 64% ORR and 91% clinical benefit rate (complete response + partial response/unconfirmed partial response + stable disease) 4% (n=3) confirmed complete responses59% (n=41) partial responses (31 confirmed and 10 unconfirmed)28% (n=19) patients with stable disease 86% (n=59) of patients had a BRAF fusion alteration, for which there are no approved systemic therapies, while the remaining 14% (n=10) had a BRAF mutation Safety data, based on 77 treated patients, indicated monotherapy tovorafenib to be generally well-tolerated. The most common side effects reported related to tovorafenib were change in hair color (75%), increased creatine phosphokinase (64%), anemia (46%), fatigue (42%) and maculopapular rash (42%). Among a total of 77 treated patients: Participants were heavily pretreated, with a median of three prior lines of systemic therapy (range: 1-9)The median duration of tovorafenib treatment was 8.4 months, with 77% (n=59) of patients on treatment at the time of the data cutoffNearly 60% (n=46) of patients had already received at least one prior MAPK inhibitor prior to study participation “The responses we’ve observed in the FIREFLY-1 study with weekly monotherapy tovorafenib in children with recurrent or progressive low-grade gliomas are very encouraging,” said Samuel Blackman, M.D., Ph.D., co-founder and chief medical officer of Day One. “As tovorafenib progresses in the clinic, we want to thank the patients, their families, the clinical investigators, and the advocates who have chosen to participate in the FIREFLY-1 clinical trial and support the development of a potential new treatment for children in need of new therapeutic options.” FIREFLY-1 is evaluating tovorafenib as once-weekly monotherapy in patients aged 6 months to 25 years with recurrent or progressive pLGG. The trial is being conducted in collaboration with the Pacific Pediatric Neuro-Oncology Consortium (PNOC) and is designed to support the potential regulatory approval of tovorafenib. “Based on the efficacy and safety profile of tovorafenib observed to date from the FIREFLY-1 trial population, we plan to submit a New Drug Application in the first half of this year that will include additional follow up from the full study population,” said Jeremy Bender, Ph.D., chief executive officer of Day One. “We look forward to continuing our discussions with regulatory authorities with the hope of bringing this therapy to children in need of new options as soon as possible.” In addition to FIREFLY-1, Day One is expanding the development of tovorafenib as a front-line therapy for patients newly diagnosed with pLGG. The global, Phase 3, registrational FIREFLY-2/LOGGIC clinical trial is evaluating once-weekly monotherapy tovorafenib in newly-diagnosed patients with pLGG harboring a known activating RAF alteration. About Pediatric Low-Grade GliomaPediatric low-grade glioma (pLGG) is the most common brain tumor diagnosed in children, accounting for 30% – 50% of all central nervous system tumors. BRAF wild-type fusions are the most common cancer-causing genomic alterations in pediatric low-grade gliomas. These genomic alterations are also found in several adult and pediatric solid tumors. Pediatric low-grade glioma can impact a child’s health in many ways depending on tumor size and location, including vision loss and motor dysfunction. There are no approved therapies for pLGG, and current treatment approaches are associated with potential acute and life-long adverse effects. While most children with pLGG survive their cancer, children who do not achieve remission following surgery may face years of increasingly aggressive therapies. Due to the indolent nature of pLGG, patients generally receive multiple years of systemic therapy. About TovorafenibTovorafenib is an investigational, oral, brain-penetrant, highly-selective type II pan-RAF kinase inhibitor designed to target a key enzyme in the MAPK signaling pathway, which is being investigated in primary brain tumors or brain metastases of solid tumors. Tovorafenib has been studied in over 325 patients to date. Currently tovorafenib is under evaluation in a pivotal Phase 2 clinical trial (FIREFLY-1) among pediatric, adolescent and young adult patients with recurrent or progressive pLGG, which is an area of considerable unmet need with no approved therapies. Tovorafenib is also being evaluated alone or as a combination therapy for adolescent and adult patient populations with recurrent or progressive solid tumors with MAPK pathway aberrations (FIRELIGHT-1). Tovorafenib has been granted Breakthrough Therapy and Rare Pediatric Disease designations by the U.S. Food and Drug Administration (FDA) for the treatment of patients with pLGG harboring an activating RAF alteration. Tovorafenib has also received Orphan Drug designation from the FDA for the treatment of malignant glioma, and from the European Commission (EC) for the treatment of glioma. About the Pacific Pediatric Neuro-Oncology ConsortiumThe Pacific Pediatric Neuro-Oncology Consortium (PNOC) is an international consortium with study sites within the United States, Canada, Europe and Australia dedicated to bringing new therapies to children and young adults with brain tumors. About Day One BiopharmaceuticalsDay One Biopharmaceuticals is a clinical-stage biopharmaceutical company that believes when it comes to pediatric cancer, we can do better. We put kids first and are developing targeted therapies that deliver to their needs. Day One was founded to address a critical unmet need: the dire lack of therapeutic development in pediatric cancer. The Company’s name was inspired by “The Day One Talk” that physicians have with patients and their families about an initial cancer diagnosis and treatment plan. Day One aims to re-envision cancer drug development and redefine what’s possible for all people living with cancer—regardless of age—starting from Day One. Day One partners with leading clinical oncologists, families, and scientists to identify, acquire, and develop important emerging cancer treatments. The Company’s lead product candidate, tovorafenib (DAY101), is an investigational, oral, brain-penetrant, highly-selective type II pan-RAF kinase inhibitor. The Company’s pipeline also includes pimasertib, an investigational, oral, highly-selective small molecule inhibitor of mitogen‐activated protein kinases 1 and 2 (MEK-1/-2). Day One is based in South San Francisco. For more information, please visit www.dayonebio.com or find the company on LinkedIn or Twitter. Cautionary Note Regarding Forward-Looking Statements This press release contains “forward-looking” statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to: Day One’s plans to develop cancer therapies, expectations from current clinical trials, the execution of the Phase 2 and Phase 3 clinical trial for tovorafenib as designed, any expectations about safety, efficacy, timing and ability to complete clinical trials, release data results and to obtain regulatory approvals for tovorafenib and other candidates in development, and the ability of tovorafenib to treat pLGG or related indications. Statements including words such as “believe,” “plan,” “continue,” “expect,” “will,” “develop,” “signal,” “potential,” or “ongoing” and statements in the future tense are forward-looking statements. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they do not fully materialize or prove incorrect, could cause our results to differ materially from those expressed or implied by such forward-looking statements. Forward-looking statements are subject to risks and uncertainties that may cause Day One’s actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties in this press release and other risks set forth in our filings with the Securities and Exchange Commission, including Day One’s ability to develop, obtain regulatory approval for or commercialize any product candidate, Day One’s ability to protect intellectual property, the potential impact of global business or macroeconomic conditions, including as a result of the COVID-19 pandemic, inflation and rising interest rates and the sufficiency of Day One’s cash, cash equivalents and investments to fund its operations. These forward-looking statements speak only as of the date hereof and Day One specifically disclaims any obligation to update these forward-looking statements or reasons why actual results might differ, whether as a result of new information, future events or otherwise, except as required by law. DAY ONE MEDIA Laura Cooper, Head of Communicationslaura.cooper@dayonebio.com DAY ONE INVESTORSHans Vitzthum, LifeSci Advisorshans@lifesciadvisors.com