On August 17, 2022 Exscientia plc (Nasdaq: EXAI) reported that Recent developments in the Company’s pipeline, collaborations, and operations, as well as financial results for the second quarter and first half 2022, are summarised below (Press release, Exscientia, AUG 17, 2022, View Source [SID1234618455]). In addition, Exscientia will host a conference call Thursday, August 18 at 1:30 p.m. BST / 8:30 a.m. ET to provide an overview of the company’s pipeline and corporate strategy.

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"In the first half of 2022, we delivered on major new and existing collaborations, advanced our pipeline programmes, and marked the 10-year anniversary of Exscientia’s founding. Over the past decade, we’ve pioneered an AI-driven approach to modernising drug discovery and development, and it was fitting that this quarter we also announced topline data from our EXS-21546 programme, one of the first AI-designed molecules to enter clinical trials," said Andrew Hopkins, D.Phil., Exscientia’s founder and Chief Executive Officer. "With over $730 million in cash, we believe we are in a strong position to deliver across our portfolio of drug projects for the long-term. Our strategy creates an agile interplay between our internal pipeline and partnered programmes, enabling us to move candidates between the two depending on the best fit for Exscientia and our partners, as well as how we can best impact the probability of success for patients."

Recent Highlights

Progress across internal and partnered pipeline, leveraging the Company’s precision medicine platform, as well as key components of Exscientia’s technology and operations.

Internal pipeline

Wholly, majority and co-owned programmes focused on areas in which Exscientia believes it can improve the probability of success, including precision oncology

Following topline data in June, the Company remains on track to initiate a Phase 1b/2 study of EXS-21546 (majority owned with Evotec) in the second half of 2022
Phase 1b/2 study will be optimised with simulation-guided clinical trial design principles as well as leverage Exscientia’s precision medicine platform to maximise potential impact to the most relevant patients
GTAEXS-617 (co-owned with GT Apeiron) CTA submission expected by year-end 2022
CTA and IND-enabling studies are ongoing, including translational work to support planned clinical trials expected to start in the first half of 2023
Partnered programmes

Utilising a scalable end-to-end platform to advance a broad pipeline, while also generating significant cash inflows to support advancements

First two targets identified in new Sanofi collaboration for oncology and inflammation & immunity, respectively
First precision medicine project initiated; focused on patient enrichment for a Sanofi biologic in oncology
Advancing Bristol Myers Squibb (BMS) collaboration with continued progress across both BMS1 and BMS2 collaborations
Following the achievement of recent successful drug discovery milestone, Exscientia and Bayer have mutually agreed to end collaboration; Exscientia will retain optionality to develop one of the two targets pursued under the collaboration
The Bayer agreement was the last Exscientia partnership based on AI-only design services, which included lower economics and reduced operational involvement in comparison with more recent partnerships
This update aligns with Company strategy to increasingly focus on programmes where Exscientia’s AI design, experimental biology and precision medicine platforms can be integrated
Recent clinical progress highlights ability of the Company’s advanced, AI-based platform to create novel molecules with high level of translatability to human biology

Announced topline data from EXS-21546 Phase 1a healthy volunteer study in June 2022
The study demonstrated that observed human pharmacokinetics for EXS-21546 were in line with what had been designed for and predicted in preclinical modelling, supporting a twice-daily (BID) dose for continuous A2A receptor inhibition over a dosing interval
EXS-21546 signalled inhibition of A2A receptor was sustained over the BID dosing period, demonstrating a level of lasting target engagement
EXS-21546 was well-tolerated with no CNS adverse events reported in the SAD portion at all doses (30mg, 90mg, 250mg, 400mg) and in the MAD portion at 150mg BID
Exscientia’s approach allows for significant cash inflows to drive the business

$111.0 million cash flow from collaborations in second quarter 2022, including $100.0 million from Sanofi, ending the first half 2022 with $732.0 million in cash, cash equivalents and short-term bank deposits
Includes constant currency mark-to-market foreign exchange impact of negative 8%
During the quarter, Exscientia recognised realised foreign exchange gains net of forward contract settlements of $14.0 million. The Company holds its deposits in both GBP and USD intended to match expected cash needs while limiting the impact of exchange rate fluctuations
Second quarter 2022 net positive cash inflows from operations of $72.9 million
Expanded leadership team in critical growth areas

Eileen Jennings-Brown joined as Exscientia’s Chief Information Officer, reporting to Garry Pairaudeau, Chief Technology Officer, and responsible for overseeing IT and DevOps. Ms. Jennings-Brown brings more than 25 years of experience across IT roles, including most recently heading technology for the Wellcome Trust.
Charlotte Deane, Ph.D., Chief Scientist of Biologics AI, who joined Exscientia in January 2022, was awarded an appointment to the Most Excellent Order of the British Empire (MBE) for leading the UK Research and Innovation’s rapid response call for projects addressing issues arising from the pandemic.
Select peer-reviewed publications and scientific meeting presentations during the quarter

"Coverage Score: A Model Agnostic Method to Efficiently Explore Chemical Space," was published in the Journal of Chemical Information and Modeling in July 2022. This advancement in active learning allows more efficient exploration of chemical space, potentially leading to increased diversity of candidates, faster model improvement and shorter time to candidate identification
"Surface Plasmon Resonance Screening to Identify Active and Selective Adenosine Receptor Binding Fragments," a study which further validates Exscientia’s innovative biosensor approach to screening wildtype GPCR targets to advance drug discovery, was published in the ACS Medicinal Chemistry Letters in June 2022
Three posters presented at the AACR (Free AACR Whitepaper) Annual Meeting in April, highlighting Exscientia’s human tissue precision medicine platform, including potential benefits of Exscientia’s AI-driven design to overcome known issues such as potency, toxicity and selectivity and improve patient outcomes
Investor call and webcast information

Exscientia will host a conference call on Thursday, August 18 at 1:30 p.m. BST / 8:30 a.m. ET. A webcast of the live call can be accessed by visiting the "Investors and Media" section of the Company’s website at investors.exscientia.ai. Alternatively, the live conference call can be accessed by dialling +1 (888) 330 3292 (U.S.), +44 203 433 3846 (U.K.), +1 (646) 960 0857 (International) and entering the conference ID: 8333895. A replay will be available for 90 days under "Events and Presentations" in the "Investors and Media" section of the Exscientia website.

Second quarter and first half 2022 financial results

For the convenience of the reader, the Company has translated pound sterling amounts to U.S. dollars at the rate of £1.000 to $1.2162, which was the noon buying rate of the Federal Reserve Bank of New York on June 30, 2022.

Revenue: Recognised revenue for the three and six months ended June 30, 2022, was $8.7 million and $17.2 million respectively, representing an increase of $8.3 million and $10.4 million compared to the three and six months ended June 30, 2021, primarily due to delivery on an increased number of projects across our second collaboration with BMS, revenues generated from the extension of the BMS agreement to leverage Exscientia’s precision medicine platform, and recognition of remaining revenues following the termination of the Bayer agreement.

R&D and cost of drug discovery: Due to various collaboration structures, expenditure incurred in relation to research and development activities may be recognised within one of several financial statement captions. The tables below show how these expenses are separated across the accounting categories.

Research and development expenses: R&D expenses for the three and six months ended June 30, 2022, were $40.2 million and $68.8 million respectively, as compared to $9.9 million and $15.1 million for the same period ended June 30, 2021. The increase in research and development expenses was in part due to the growth of Exscientia’s internal and co-owned portfolio, in addition to increased headcount and other costs associated with the Company’s continued technology investments. Share-based compensation accounted for $9.1 million and $12.1 million for the quarter and half year ended June 30, 2022, as compared to $1.6 million and $1.9 million for the same period ended June 30, 2021.

General and administrative expenses: G&A expenses for the three and six months ended June 30, 2022, were $14.7 million and $24.2 million respectively, or 22.3% and 21.9% respectively of total operating expenses. For the three and six months ended June 30, 2022, G&A expenses increased by $5.6 million and $11.1 million compared to the three and six months ended June 30, 2021, primarily associated with an increase in personnel costs and additional costs incurred in relation to the operation of a listed company. Share-based compensation accounted for $3.3 million and $4.6 million for the quarter and half year ended June 30, 2022, as compared to $1.7 million and $2.0 million for the same periods ended June 30, 2021.

Cash inflows: For the second quarter 2022, Exscientia received $111.0 million in cash inflows from its collaborations as compared to $39.5 million during the second quarter 2021.

Cash, cash equivalents and bank deposits: Cash, cash equivalents and bank deposits as of June 30, 2022, were $732.0 million as compared to $683.7 million as of December 31, 2022. This includes a 12-month fixed term deposit of $121.7 million.

On August 17, 2022 Scandion Oncology (Scandion), a biotech company developing first-in-class medicines aimed at treating cancer which is resistant to current treatment options, reported that it has observed a better-than-expected tolerability of its potential new cancer treatment SCO-101 in the dose-finding PANTAX phase 1b-trial (Press release, Scandion Oncology, AUG 17, 2022, View Source,c3615032 [SID1234618452]). Thus, dosing is now escalated to higher levels than expected based on the initial findings in the CORIST trial, which prompted the amendment of the PANTAX trial design communicated in January 2021.

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The continued dose escalation extends the PANTAX trial meaning it is now expected to read out in the first half of 2023 (previously expected in the third quarter of 2022). Trial execution is strong with good patient recruitment and the trial is progressing well.

PANTAX is a dose-finding phase Ib-trial in patients with unresectable or metastatic pancreatic

cancer who are offered SCO-101 as an add-on therapy to their standard chemotherapy. The good tolerability of SCO-101 observed in this setting supports the overall profile of the compound as well tolerated in vulnerable patients.

"We have been positively surprised by the tolerability of SCO-101 observed in this trial, which further supports our belief in the potential of SCO-101 as a new cancer treatment improving options for patients. Naturally, we continue the dose escalation beyond our expectations in order to find the optimal dose of SCO-101 in this indication and combination, even if this of course postpones the readout from the trial", says Bo Rode Hansen, President & CEO of Scandion.

Scandion is also currently carrying out the CORIST phase 2-trial in which SCO-101 is studied as combination therapy in patients with metastatic colorectal cancer. Topline data from the ongoing second part of this trial is still expected during the third quarter of 2022.

On August 17, 2022 GSK plc (LSE/NYSE: GSK) reported that the US Food and Drug Administration (FDA) accepted the New Drug Application (NDA) for momelotinib, a potential new medicine with a proposed differentiated mechanism of action that may address the significant unmet medical needs of myelofibrosis patients with anaemia (Press release, GlaxoSmithKline, AUG 17, 2022, View Source [SID1234618451]). The US FDA has assigned a Prescription Drug User Fee Act action date of 16 June 2023.

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The NDA is based on the results from key phase III trials, including the pivotal MOMENTUM trial, which met all primary and key secondary endpoints, including Total Symptom Score (TSS), Transfusion Independence (TI) rate and Splenic Response Rate (SRR). The primary analysis data from the MOMENTUM trial were recently presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Hybrid Congress.

Momelotinib is not currently approved in any market.

About the pivotal MOMENTUM phase III clinical trial

MOMENTUM is a global, randomised, double-blind phase III clinical trial of momelotinib versus danazol in patients with myelofibrosis who were symptomatic and anaemic and had been previously treated with an FDA-approved JAK inhibitor. The trial was designed to evaluate the safety and efficacy of momelotinib for treating and reducing key hallmarks of the disease: symptoms, blood transfusions (due to anaemia) and splenomegaly (enlarged spleen).

The trial’s primary efficacy endpoint was TSS reduction of ≥50% over the 28 days immediately before the end of Week 24 compared to baseline TSS, using the Myelofibrosis Symptom Assessment Form. Key secondary endpoints included TI rate for ≥12 weeks immediately before the end of Week 24 with haemoglobin levels ≥ 8 g/dL and SRR based on splenic volume reduction of ≥35% at Week 24 from baseline.

Patients were randomised at 2:1 to receive either momelotinib or danazol (n=130 and n=65, respectively). After 24 weeks of treatment, patients on danazol were allowed to crossover to receive momelotinib. Early crossover to momelotinib was available for confirmed splenic progression. The trial enrolled 195 patients across 21 countries.

About momelotinib

Momelotinib is a potential new medicine with a differentiated mechanism of action, with inhibitory ability along three key signalling pathways: Janus kinase (JAK) 1, and JAK2 and activin A receptor, type I (ACVR1).1,2,3,4 Inhibition of JAK1 and JAK2 may improve constitutional symptoms and splenomegaly.1,2,4 Additionally, direct inhibition of ACVR1 leads to a decrease in circulating hepcidin, which is elevated in myelofibrosis and contributes to anaemia.1,2,3,4

Momelotinib was most recently developed by Sierra Oncology, Inc., which GSK acquired in July 2022, building on GSK’s expertise in haematology and portfolio of specialty medicines and vaccines.

About myelofibrosis

Myelofibrosis is a rare blood cancer that results from dysregulated JAK-signal transducer and activator of transcription protein signalling and is characterised by constitutional symptoms, splenomegaly, and progressive anaemia. Myelofibrosis affects approximately 20,000 patients in the US, with about 40% of patients already anaemic at the time of diagnosis and nearly all patients estimated to develop anaemia eventually.1,5 Patients will often require transfusions, and more than 30% will discontinue treatment due to anaemia.6 Anaemia and transfusion dependence strongly correlate with poor prognosis and shortened survival.7

GSK in oncology

GSK is focused on maximising patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, cell therapy, tumour cell targeting therapies and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody-drug conjugates, and cell therapy, either alone or in combination.

On August 17, 2022 Bristol Myers Squibb (NYSE:BMY) reported that it has successfully completed its acquisition of Turning Point Therapeutics, Inc. ("Turning Point"), in an all-cash transaction (Press release, Bristol-Myers Squibb, AUG 17, 2022, View Source [SID1234618449]). With the completion of the acquisition, Turning Point shares have ceased trading on the NASDAQ Global Select Market and Turning Point is now a wholly owned subsidiary of Bristol Myers Squibb.

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"Turning Point has distinguished itself in the field of precision oncology, and this acquisition will further strengthen our leading oncology franchise," said Elizabeth Mily, Executive Vice President, Strategy & Business Development, Bristol Myers Squibb. "With Turning Point’s lead asset, repotrectinib, Bristol Myers Squibb will be positioned to address a significant unmet medical need for ROS1-positive non-small cell lung cancer patients. We look forward to bringing this promising, innovative medicine to patients in the second half of 2023."

Through the transaction, Bristol Myers Squibb gains a pipeline of investigational medicines designed to target the most common mutations associated with oncogenesis, including repotrectinib. Repotrectinib is a next-generation, potential best-in-class tyrosine kinase inhibitor targeting the ROS1 and NTRK oncogenic drivers of non-small cell lung cancer (NSCLC) and other advanced solid tumors. In the Phase 1/2 TRIDENT-1 clinical trial, longer duration of response has been observed in the landmark analysis with repotrectinib than with existing ROS1 agents in first-line NSCLC. The asset has been granted three Breakthrough Therapy Designations from the U.S. Food and Drug Administration.

Bristol Myers Squibb expects repotrectinib to be approved in the U.S. in the second half of 2023 and become a new standard of care for patients with ROS1-positive NSCLC in the first-line setting. Bristol Myers Squibb also plans to continue to explore the potential of Turning Point’s promising pipeline of novel compounds.

Bristol Myers Squibb’s previously announced tender offer for all outstanding shares of common stock of Turning Point for $76.00 per share expired at 5:00 p.m. Eastern Time on August 15, 2022. Approximately 41,896,678 shares of Turning Point common stock were validly tendered, and not validly withdrawn from the tender offer, representing approximately 84% of Turning Point’s issued and outstanding shares of common stock. In accordance with the terms of the tender offer, all shares that were validly tendered and not validly withdrawn have been accepted for payment and Bristol Myers Squibb expects to promptly pay for all such shares.

Following completion of the tender offer, Bristol Myers Squibb completed the acquisition of Turning Point through the merger of its wholly owned subsidiary, Rhumba Merger Sub Inc., with and into Turning Point, without a vote of Turning Point’s stockholders pursuant to Section 251(h) of the General Corporation Law of the State of Delaware. As a result of the merger, each share of common stock of Turning Point issued and outstanding and not tendered in the tender offer was automatically converted into the right to receive an amount in cash equal to $76.00, without interest, subject to any applicable withholding of taxes, the same price offered in the tender offer.

Turning Point shareholders can direct questions regarding the tender offer to MacKenzie Partners, Inc., the information agent for the tender offer, toll free, at 1-800-322-2885.

Advisors

Gordon Dyal & Co., LLC, is serving as the exclusive financial advisor to Bristol Myers Squibb, and Kirkland & Ellis, LLP, is serving as legal counsel. Goldman Sachs & Co., LLC, is serving as the exclusive financial advisor to Turning Point Therapeutics, and Cooley, LLP, is serving as legal counsel.

On August 17, 2022 Blueprint Medicines Corporation (NASDAQ: BPMC) reported positive top-line results from the registrational Part 2 of the PIONEER clinical trial of AYVAKIT (avapritinib) in patients with non-advanced systemic mastocytosis (SM) demonstrating clinically meaningful and highly significant improvements across the primary and all key secondary endpoints, including patient-reported symptoms and objective measures of mast cell burden (Press release, Blueprint Medicines, AUG 17, 2022, View Source [SID1234618448]). Based on these top-line data, Blueprint Medicines plans to submit a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration (FDA) for AYVAKIT in non-advanced SM in the fourth quarter of 2022, with a subsequent submission of a type II variation marketing authorization application to the European Medicines Agency (EMA) anticipated in 2023. In addition, Blueprint Medicines plans to present detailed data from the PIONEER trial at an upcoming medical meeting.

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The trial, which was designed to assess AYVAKIT plus best available care versus placebo plus best available care (control arm), achieved its primary endpoint with a highly significant difference in the mean change in total symptom score (TSS) at 24 weeks (p=0.003). TSS was assessed by the Indolent SM Symptom Assessment Form (ISM-SAF). The AYVAKIT arm had a reduction of 15.6 points in mean TSS at 24 weeks, which continued to deepen to 20.2 points at 48 weeks in patients who rolled over to the Part 3 open-label extension study. At 24 weeks, the control arm had a reduction of 9.2 points in mean TSS. In addition, the PIONEER trial met all key secondary endpoints, including significant improvements across all measures of mast cell burden. More than half of AYVAKIT-treated patients had a ≥50 percent reduction of serum tryptase, compared to no patients in the control arm (53.9% vs. 0%; p<0.0001). AYVAKIT was well-tolerated and had a favorable safety profile, and 96.5 percent of AYVAKIT-treated patients completed 24 weeks of therapy, compared to 93.0 percent for the control arm. Overall, 0.7 percent of patients in the AYVAKIT arm and no patients in the control arm discontinued due to treatment-related adverse events.

"As a physician and clinical researcher who has been treating non-advanced systemic mastocytosis patients for over 25 years, I have been awaiting a therapy that decreases the abnormal mast cell burden and activation, improves a wide range of symptoms, and ultimately provides an improved quality of life to patients," said Mariana Castells, M.D., Ph.D., Director, Mastocytosis Center, Brigham and Women’s Hospital, and an investigator on the PIONEER trial. "For patients with non-advanced SM, PIONEER is the first study to show significant clinical improvements over best available care across patient-reported symptoms and objective measures of disease, with a safety and tolerability profile supporting chronic treatment. The trial results suggest that if approved, AYVAKIT would represent a practice-changing treatment, enabling important clinical benefits for a broad range of patients with non-advanced SM."

"The PIONEER results showcase Blueprint Medicines’ dedication to advancing the promise of precision therapy for patients with significant medical needs," said Becker Hewes, M.D., Chief Medical Officer at Blueprint Medicines. "AYVAKIT has the potential to be the first approved medicine for non-advanced SM, and the only treatment that would address the genetic root cause across advanced and non-advanced forms of the disease. Today’s milestone represents a watershed moment for the systemic mastocytosis community and Blueprint Medicines, capping a decade of collaboration with clinicians, advocates and patients to transform standards of care, and to deepen the understanding of this disease and its impact on various aspects of patients’ lives."

AYVAKIT was designed to potently and selectively inhibit D816V mutant KIT, the driver of SM in about 95 percent of cases. SM often leads to debilitating skin, gastrointestinal, neurocognitive and other systemic symptoms, such as life-threatening anaphylaxis.

"Non-advanced systemic mastocytosis is a lifelong disease with severe physical, emotional and social impacts that profoundly reduce patients’ quality of life," said Lauren Denton, Executive Director of The Mast Cell Disease Society. "Patients with SM continue to be challenged by efforts to avoid various triggers of everyday life while also managing complex therapies. The PIONEER clinical trial results offer hope to these patients and help pave the way for new innovation in treatment."

"These new data are the culmination of a dedicated long-term collaboration and shared ‘patients first’ core value between Blueprint Medicines and The Mast Cell Disease Society. We are excited by these results and further energized to work together with these exceptional investigators to transform the lives of patients, offering them a better quality of life and the gift of time," said Valerie Slee, Board Chair of The Mast Cell Disease Society.

Top-line Data from the PIONEER Trial

Part 2 of the registrational PIONEER trial was designed to evaluate the efficacy and safety of AYVAKIT (25 mg once-daily dosing; N=141) versus control (N=71) over 24 weeks of treatment. Eligibility criteria include an indolent SM diagnosis confirmed by central pathology review, and moderate-to-severe symptom burden despite an optimized regimen of best available care. Patients were able to continue symptom-directed therapies while receiving AYVAKIT or placebo. Results were reported as of a data cutoff date of June 23, 2022.

Baseline data, including mean TSS, were consistent with Part 1 of the trial. The PIONEER study achieved its primary endpoint and all key secondary endpoints, with AYVAKIT showing highly significant improvements in patient-reported symptoms and objective measures of disease burden.

Clinical Outcome Measures: AYVAKIT Arm vs. Control Arm P-valuea
Primary Endpoint Mean Change in TSS p=0.003
Secondary Endpointsb

≥30% Reduction in Mean TSS p=0.009
≥50% Reduction in Mean TSS p=0.005
Mean Change in Most Severe Symptom Score p=0.015
≥50% Reduction in Serum Tryptase p<0.0001
≥50% Reduction in KIT D816V Variant Allele Fraction p<0.0001
≥50% Reduction in Bone Marrow Mast Cell Aggregates p<0.0001

a One-sided p-value <0.025 indicates statistical significance.

b For secondary endpoints, reductions in TSS and objective measures of mast cell burden represent proportion of patients with ≥30% and ≥50% reductions. All endpoints are key secondary endpoints, except for mean change in most severe symptom score, which is an additional secondary endpoint.

AYVAKIT had a favorable safety profile compared to the control arm. The rate of adverse events (AEs) was 90.8 percent in the AYVAKIT arm and 93.0 percent in the control arm. Serious AEs occurred in 5.0 percent of AYVAKIT-treated patients, compared to 11.3 percent of patients in the control arm. Discontinuations due to treatment-related AEs occurred in 0.7 percent of AYVAKIT-treated patients and 0 percent of patients in the placebo arm. The AYVAKIT arm had a lower rate of cognitive AEs than the control arm (2.8% AYVAKIT vs. 4.2% control), and there were no intracranial bleeding events. Treatment-related AEs reported in at least three patients in either arm and at least 5 percent of AYVAKIT-treated patients included headache (7.8% AYVAKIT vs. 9.9% control), nausea (6.4% AYVAKIT vs 8.5% control), peripheral edema (6.4% AYVAKIT vs. 1.4% control) and periorbital edema (6.4% AYVAKIT vs. 2.8% control). In the AYVAKIT arm, 93.0 percent of edema AEs were Grade 1 and the remainder were Grade 2.

Conference Call Information

Blueprint Medicines will host a live conference call and webcast at 8:00 a.m. ET today to discuss the top-line data from the PIONEER trial. The conference call may be accessed by dialing 844-200-6205 (domestic) or 929-526-1599 (international), and referring to conference ID 806215. A webcast of the call will also be available under "Events and Presentations" in the Investors & Media section of the Blueprint Medicines website at View Source The archived webcast will be available on the Blueprint Medicines website approximately two hours after the conference call and will be available for 30 days following the call.

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. The FDA granted breakthrough therapy designation to AYVAKIT for the treatment of moderate to severe indolent SM.

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 primarily driven by the KIT D816V mutation. Uncontrolled proliferation and activation of mast cells result in chronic, severe and often unpredictable symptoms for patients across the spectrum of SM. The vast majority of those affected have non-advanced (indolent or smoldering) SM, with debilitating symptoms that lead to a profound, negative impact on quality of life. 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. Across advanced SM subtypes, the median overall survival is approximately 3.5 years in ASM, approximately two years in SM-AHN and less than six months in MCL.

Debilitating symptoms, including anaphylaxis, maculopapular rash, pruritis, diarrhea, brain fog, fatigue and bone pain, often persist across all forms of SM despite treatment with a number of symptom-directed therapies. 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. Historically, there had been no approved therapies for the treatment of SM that selectively inhibit D816V mutant KIT.

About the PIONEER Trial

PIONEER is a randomized, double-blind, placebo-controlled, registrational trial evaluating AYVAKIT in patients with non-advanced SM. The trial includes three parts: dose-finding Part 1, registrational Part 2 and long-term treatment Part 3. Key trial endpoints include the change in patient-reported disease symptoms as measured by the ISM-SAF TSS, patient-reported quality of life, quantitative measures of mast cell burden and safety. Patients who completed Part 1 or 2 were eligible to participate in Part 3. All patients receive AYVAKIT treatment during Part 3, including those rolling over from the control arm. For more information about the PIONEER trial, please visit www.clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT03731260).