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Item 7.01 Regulation FD.
On April 8, 2022, Blueprint Medicines Corporation (the “Company”) is hosting an investor conference call and webcast to review data presented at the American Association for Cancer Research (“AACR”) Annual Meeting 2022 for multiple research- and clinical-stage programs across its precision oncology and hematology portfolio. A copy of the presentation from the investor conference call and webcast is furnished as Exhibit 99.1 to this Current Report on Form 8-K.
The information in Item 7.01 of this Current Report on Form 8-K, including Exhibit 99.1 attached hereto, is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.
Item 8.01 Other Events.
On April 8, 2022, the Company issued a press release announcing data for multiple research- and clinical-stage programs across its precision oncology and hematology portfolio from various poster presentations at the AACR Annual Meeting 2022. A copy of the press release is filed herewith as Exhibit 99.2 to this Current Report on Form 8-K and incorporated herein by reference.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits.
| Exhibit No. | Description | |
| 99.1 | Corporate slide presentation of Blueprint Medicines Corporation dated April 8, 2022 | |
| 99.2 | Press release issued by Blueprint Medicines Corporation on April 8, 2022 | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document and incorporated as Exhibit 101) |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| BLUEPRINT MEDICINES CORPORATION | ||
| Date: April 8, 2022 | By: |
/s/ Kathryn Haviland |
| Kathryn Haviland | ||
| Chief Executive Officer | ||
Exhibit 99.1
Precision that Moves Diane L. Patient with EGFR - driven lung cancer
Blueprint Medicines call participants 2 Introduction and portfolio overview Kate Haviland Chief Executive Officer Initial data from the SYMPHONY trial of BLU - 945 presented at the AACR Annual Meeting 2022 David Spigel, M.D. Chief Scientific Officer Sarah Cannon Research Institute Portfolio strategy and next steps Fouad Namouni, M.D. President, Research and Development Q&A All PREPARED REMARKS AACR, American Association of Cancer Research Not for promotional use.
Forward - looking statements 3 This presentation contains forward - looking statements as defined in the Private Securities Litigation Reform Act of 1995 , as amended . 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 . In this presentation, forward - looking statements include, without limitation, express or implied statements regarding plans, strategies, timelines and expectations for the current or future approved drugs and drug candidates of Blueprint Medicines Corporation (the “Company”), including timelines for the initiation of clinical trials and trial cohorts, the results of ongoing and planned clinical trials, data publications, marketing applications and approvals ; the anticipated benefits of the preclinical profiles of the Company's drug candidates ; the Company’s plans, strategies and timelines for the development of the Company’s drug candidates as monotherapies and combination with other agents ; anticipated indications for the Company's drug candidates ; plans and timelines for additional marketing applications for avapritinib and pralsetinib and, if approved, commercialization of avapritinib and pralsetinib in additional indications or in additional geographies ; the potential benefits of any of the Company’s current or future approved drugs or drug candidates in treating patients ; the Company’s scientific platform expansion plans and plans to announce new research programs ; and ௗ the Company’s ௗ financial performance, strategy, goals and anticipated milestones, business plans and focus . The Company has based these forward - looking statements on management's current expectations, assumptions, estimates and projections . If such expectations, assumptions, estimates and projections do not fully materialize or prove incorrect, the events or circumstances referred to in the forward - looking statements may not occur . While the Company believes these expectations, assumptions, estimates and projections are reasonable, such forward - looking statements are only predictions and involve known and unknown risks, uncertainties and other important factors, many of which are beyond the Company's control and may cause actual results, performance or achievements to differ materially from those expressed or implied by any forward - looking statements . These risks and uncertainties include, without limitation, risks and uncertainties related to the impact of the COVID - 19 pandemic to the Company's business, operations, strategy, goals and anticipated milestones, including the Company's 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 drugs, and launching, marketing and selling current or future approved drugs ; the Company’s ability and plans in establishing a commercial infrastructure, and successfully launching, marketing and selling current or future approved products ; the Company’s ability to successfully expand the approved indications for AYVAKIT® /AYVAKYT® (avapritinib) and GAVRETO® (pralsetinib) 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 the Company's drug candidates or the licensed drug candidate ; the Company's advancement of multiple early - stage efforts ; the Company's ability to successfully demonstrate the efficacy and safety of its drug candidates and gain approval of its drug candidates on a timely basis, if at all ; the timing and results of preclinical and clinical studies for the Company's 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 ; actions or decisions of regulatory agencies or authorities, which may affect the initiation, timing and progress of clinical trials or marketing applications ; the Company's ability to obtain, maintain and enforce patent and other intellectual property protection for AYVAKIT/AYVAKYT, GAVRETO or any drug candidates it is developing ; the Company's ability to develop and commercialize companion diagnostic tests for any of the Company's current or future approved drugs or drug candidates ; the Company’s ability to successfully expand its operations and scientific platform and the costs thereof ; the Company's ability to realize the benefits of its executive leadership transition plan ; and the success of the Company's current and future collaborations, partnerships and licenses . These and other risks and uncertainties are described in greater detail under "Risk Factors" in the Company's filings with the Securities and Exchange Commission ("SEC"), including its most recent Annual Report on Form 10 - K, as supplemented by its most recent Quarterly Report on Form 10 - Q, and any other filings it has made or may make with the SEC in the future . The Company cannot guarantee future results, outcomes, levels of activity, performance, developments, or achievements, and there can be no assurance that its expectations, intentions, anticipations, beliefs, or projections will result or be achieved or accomplished . The forward - looking statements in this presentation are made only as of the date hereof, and except as required by law, the Company undertakes no obligation to update any forward - looking statements contained in this presentation as a result of new information, future events or otherwise . Accordingly, readers are cautioned not to place undue reliance on these forward - looking statements . This presentation also contains estimates, projections and other statistical data made by independent parties and by the Company relating to market size and growth and other data about the Company's industry . These data involve a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates . In addition, projections, assumptions and estimates of the Company's future performance and the future performance of the markets in which the Company operates are necessarily subject to a high degree of uncertainty and risk . Blueprint Medicines, AYVAKIT, AYVAKYT, GAVRETO and associated logos are trademarks of Blueprint Medicines Corporation. Not for promotional use.
Blueprint Medicines is poised for growth in 2022 and beyond * Cash, cash equivalents and investments as of December 31, 2021. 4 STRONG FINANCIAL POSITION WITH ~$1B CASH AT YEAR - END 2021* Advance our clinical - stage pipeline targeting difficult - to - treat and prevalent cancer drivers Transform the lives of patients with systemic mastocytosis by improving treatment options across the spectrum disease Harness our research engine to bring forward new precision oncology and hematology programs Not for promotional use. KEY GOALS
Increasing tumor resistance and complexity drives disease progression, with no approved therapies after 1L standard of care osimertinib Approximate patient numbers covering major markets – US, EU4, UK, and Japan. 1. Excludes rare mutations including exon 20 insert ions. Internal estimates adapted from Ramalingam, et al. NEJM, 2020; Decision Resources Group: NSCLC Forecast and Epidemiology; and Harrison Se minars in Cancer Biology, 2020. Ex19del, exon 19 deletion mutations; CNS, central nervous system; OS, overall survival; PFS, progressio n f ree survival. 5 Not for promotional use. EGFR - MUTANT NSCLC ESTIMATED INCIDENT PATIENTS PER YEAR >70% OF PATIENTS PROGRESS TO 2L ~59,000 PATIENTS 1 Ex19del: ~33,000 L858R: ~26,000 1L 2L+ ~43,000 PATIENTS Ex19del: ~24,000 L858R: ~19,000 On - target resistance (e.g., C797S, T790M) Off - target/unknown resistance Lower OS and PFS in patients with L858R activating mutation On - and off - target resistance increasingly emerges CNS is a common site of disease progression CHALLENGES
Opportunities for our next - generation EGFR precision therapies Approximate patient numbers covering major markets – US, EU4, UK, and Japan. 1. Excludes rare mutations including exon 20 insert ions. Internal estimates adapted from Ramalingam, et al. NEJM, 2020; Decision Resources Group: NSCLC Forecast and Epidemiology; and Harrison Seminars in Cancer Biology, 2020. CNS, central nervous system. 6 Not for promotional use. EGFR - MUTANT NSCLC ESTIMATED INCIDENT PATIENTS PER YEAR >70% OF PATIENTS PROGRESS TO 2L ~59,000 PATIENTS 1 Ex19del: ~33,000 L858R: ~26,000 1L 2L+ ~43,000 PATIENTS Ex19del: ~24,000 L858R: ~19,000 On - target resistance (e.g., C797S, T790M) Off - target/unknown resistance Enhance activity on L858R activating mutation Prevent or treat on - target resistance Treat off - target resistance with well - tolerated combos OPPORTUNITIES Prevent or treat brain mets with enhanced CNS penetration
Our portfolio of EGFR therapies are purpose - built to address medical needs CS, C797S resistance mutation; Ex20in, activating exon 20 insertion mutations; LR, L858R activating mutation; TM, T790M resis tan ce mutation. 7 Not for promotional use. Effectively block the EGFR pathway Establish 2L+ SOC with combinations that treat on - and off - target resistance TREATMENT GOALS • Potent EGFR mutation coverage: o LR and LR/CS o TM and TM/CS regardless of activating mutation o Potential for broader coverage at higher exposures • Highly selective over wild - type EGFR • Potent EGFR mutation coverage: o Ex19del and LR o CS regardless of activating mutation • Highly CNS penetrant BLU - 451 • Potent inhibitor of all common Ex20ins • Highly selective over wild - type EGFR • CNS penetrant BLU - 701 BLU - 945 BLUEPRINT MEDICINES EGFR PORTFOLIO
Emerging evidence of activity of BLU - 945 in patients with advanced EGFR - mutant NSCLC utilizing circulating tumor DNA in the Phase 1/2 SYMPHONY study American Association for Cancer Research Annual Meeting 2022 April 8, 2022 Elaine Shum, Yasir Elamin, Karen L Reckamp, Zofia Piotrowska, Julie Rotow, Daniel SW Tan, Koichi Goto, Jagan Parepally, Faris Albayya, Melinda Louie - Gao, Renata Sawtell, Alena Zalutskaya, David Spigel
Disclosures Dr. David Spigel, MD, Chief Scientific Officer, Sarah Cannon Research Institute • Research funding : Aeglea Biotherapeutics, Agios, Apollomics, Arcus, Arrys Therapeutics, Astellas, AstraZeneca, Bayer, BeiGene, BIND Therapeutics, BioNTech RNA Pharmaceuticals, Blueprint Medicines, Boehringer - Ingelheim, Bristol - Myers Squibb, Calithera, Celgene, Celldex, Clovis, Cyteir Therapeutics, Daiichi Sankyo, Denovo Biopharma, Eisai, Elevation Oncology, EMD Serono, Evelo Biosciences, GI Therapeutics, Roche/Genentech, GlaxoSmithKline, GRAIL, Hutchison MediPharma, ImClone Systems, Incyte, ImmunoGen, Ipsen, Janssen, Kronos Bio, Eli Lilly, Loxo Oncology, MacroGenics, MedImmune, Merck, Molecular Partners, Molecular Template, Nektar, Neon Therapeutics, Novartis, Novocure, Oncologie, Pfizer, PTC Therapeutics, PureTech Health, Razor Genomics, Repare Therapeutics, Rgenix, Takeda, Tesaro, Tizona Therapeutics, Transgene, UT Southwestern, Verstem • Consulting/advisory : Amgen, AstraZeneca, Bristol - Myers Squibb, Curio Science, EMD Serono, Evidera, Exelixis, GlaxoSmithKline, Intellisphere, Ipsen, Janssen, Jazz, Lilly, Mirati Therapeutics, Molecular Templates, Novartis, Novocure, Pfizer, Puma Biotechnology, Regeneron Pharmaceuticals, Roche/Genentech, Sanofi - Aventis *All payments made to Sarah Cannon Research Institute
Combinations are needed to prevent and treat mutational heterogeneity, and prolong patient benefit in EGFR mutant NSCLC 1. Supplemental data in Soria et al NEJM 2018. Ramalingam et al NEJM 2020. 2. Leonetti, et al. British Journal of Cancer, 201 9. 1L, first - line; 2L, second - line; 3L, third - line; 1G, first - generation; 2G, second - generation; 3G, third - generation; mPFS, median progression free survival; mOS, median overall survival. 10 Osimertinib prolongs PFS and OS… …but patients with L858R have worse outcomes versus exon 19 deletion FLAURA study in 1L EGFRm NSCLC osimertinib median PFS and OS 1 In addition, resistance inevitably emerges… …with C797X and T790M the most common EGFR resistance mutations 2 Off - target resistance may occur independently or co - occur with EGFR resistance Estimated frequency of EGFR resistance mPFS mOS 14.4 months 21.4 months 32 months 42 months L858R Ex19del Not for promotional use. 1L 2L +T790M: ~60% 1G +C797X: ~25% 3G No approved therapy 3L +C797X: ~10% 3G Data post 1L 3G are immature No approved therapy
BLU - 945 potency and selectivity enable wide therapeutic index and broad EGFR coverage, including activating L858R mutation BLU - 945’s therapeutic index enables potent inhibition of EGFR mutants compared to SOC therapies 1 BLU - 945 is active alone in combination with BLU - 701 in an osimertinib - resistant L858R/C797S CDX model 2 11 1. Company data on file. IC 50 measured by pEGFR in cells. 2. Data presented at AACR annual meeting 2022. Abstract #3328. Not for promotional use. L 8 5 8 R L 8 5 8 R / C 7 9 7 S L 8 5 8 R / T 7 9 0 M L 8 5 8 R / T 7 9 0 M / C 7 9 7 S E x 1 9 d e l / T 7 9 0 M / C 7 9 7 S 1 10 100 1000 R a t i o : W T I C 5 0 / M u t a n t I C 5 0 BLU-945 osimertinib gefitinib
SYMPHONY first - in - human clinical trial of BLU - 945 a Based on Bayesian Optimal Interval escalation design (BOIN); b BID dosing will also be evaluated; c Part 1B and Phase 2 have not been initiated and are dependent on Part 1A results. ctDNA, circulating tumor DNA; DUSP6, dual specificity phosphatase 6; ECOG PS, Eastern Cooperative Oncology Group performance status; EGFRm, muta nt epidermal growth factor receptor gene; PK, pharmacokinetics; MTD, maximum tolerated dose; NSCLC, non - small cell lung cancer; ORR, overall response rate; Osi; osimertinib; RP2D, recommended phase 2 dose; SPRY4, sprouty RTK signaling antagonist 4; TKI, tyrosine kinase inhibitor. 12 Not for promotional use. Key eligibility • Age > 18 years • Metastatic EGFRm NSCLC • Prior treatment with > 1 TKI • No known additional tumor drivers • ECOG PS 0 – 1 Monotherapy Escalation a,b • 25 – 400 mg (n=33) • 600 mg dosing ongoing • MTD not reached Combination Escalation c BLU - 945 + Osimertinib Planned starting dose • 80 mg Osi + 200 mg BLU - 945 Primary endpoints MTD, RP2D, Safety Key secondary endpoints ctDNA kinetics, PK, ORR DUSP6 and SPRY4 modulation BLU - 945 + OSIMERTINIB EXPANSION COHORTS BLU - 945 MONOTHERAPY EXPANSION COHORTS
Demography and baseline characteristics a Original study protocol permitted ECOG PS of 0 – 2, but was later amended to ECOG PS of 0 – 1; b Patients with EGFR - mutant NSCLC are enrolled based on local mutation assessment of tumor biopsy or blood ctDNA with central ctDNA assessment at C1D1; c Results for all patients were not available at the time of the data cut. C, cycle; ctDNA NGS, circulating tumor DNA next gene rat ion sequencing; D, day; ECOG PS, Eastern Cooperative Oncology Group performance status; EGFRm, primary EGFR activating mutation, exon 19 deletion or L858R . A s of the data cut - off (March 9, 2022), 33 patients have been treated with BLU - 945 at 25 – 400 mg once daily (QD) in the first 5 cohorts. 13 Not for promotional use. • As of the data cut - off, ~33 patients treated with BLU - 945 at 25 – 400 mg once daily (QD) and dose escalation is ongoing • Most patients were non - smokers and the majority (n=26 [79%]) had received ≥3 lines of prior systemic therapy Characteristic All patients (N=33) Median age (range), years 61 (39 – 78) Female, n (%) 23 (70) Race, n (%) White 14 (42) Asian 18 (55) Other/unknown 1 (3) Smoking history, n (%) Current/former 10 (30) Never 22 (67) Unknown 1 (3) ECOG PS, n (%) a 0 8 (24) 1 23 (70) 2 2 (6) History of CNS disease, n (%) 21 (64) Prior therapy, median (range) 4 (1 – 9) Prior osimertinib 32 (97) 1 - 2 7 (21) ≥ 3 26 (79) Characteristic All patients (N=33) EGFR mutation status at C1D1 by central ctDNA NGS assessment b , n (%) EGFRm/T790M/C797S 11 (33) EGFRm/T790M 1 (3) EGFRm/C797S 1 (3) EGFRm primary only 6 (18) T790M only 1 (3) No EGFR mutations detected 9 (27) Not available c 4 (12)
BLU - 945 was generally well - tolerated in the ongoing Phase 1 trial 14 AE, adverse event; DLT, dose - limiting toxicity; MTD, maximum tolerated dose. As of the data cut - off (March 9, 2022), 33 patients have been treated with BLU - 945 at 25 – 400 mg once daily (QD) in the first 5 cohorts. Not for promotional use. AEs, regardless of causality, n (%) All AEs N=33 Treatment - related AEs N=33 Any grade Grade 3 Any grade Grade 3 Nausea 10 (30) 2 (6) 7 (21) 1 (3) Headache 6 (18) 2 (6) 1 (3) 0 Fatigue 6 (18) 0 5 (15) 0 Cough 5 (15) 0 1 (3) 0 Dyspnea 5 (15) 1 (3) 0 0 Vomiting 5 (15) 1 (3) 3 (9) 1 (3) Hyponatremia 4 (12) 0 0 0 Dry Mouth 4 (12) 0 3 (9) 0 Anemia 4 (12) 1 (3) 0 0 • No Grade 4 or 5 AEs • One DLT, grade 3 transaminitis, in 400 mg QD cohort ▪ Improved with dose interruption; patient remains on therapy • AEs associated with EGFR wild - type inhibition were minimal • No interstitial lung disease or QTc prolongation • 8 (24%) serious AEs, with 2 (6%) deemed to be related: ▪ Grade 3 vomiting ▪ Grade 3 transaminitis • No treatment discontinuations due to AEs • Dose escalation continues and the MTD has not yet been determined Most common AEs by preferred term in ≥10% of patients
BLU - 945 exposure showed increasing IC 90 coverage of activating and resistance mutations at higher doses Dashed lines represent IC 90 for indicated EGFR mutants. C, Cycle; D, day; QD, once daily. As of the data cut - off (March 9, 2022), 33 patients have been tre ated with BLU - 945 at 25 – 400 mg once daily (QD) in the first 5 cohorts. 15 Not for promotional use. C1D1 C1D15 25 mg 50 mg 100 mg 200 mg 400 mg ex19del +/ – C797S EGFRm/T790M +/ – C797S 1 10 100 1000 10000 0 6 12 18 24 Time (hours) L858R +/ – C797S BLU - 945 concentration (ng/mL) 10000 1 10 100 1000 ex19del +/ – C797S L858R +/ – C797S EGFRm/T790M +/ – C797S 0 6 12 18 24 Time (hours) • Exposure at 400 mg exceeds: ▪ EGFRm/T790M +/− C797S IC 90 in all patients ▪ L858R +/− C797S IC 90 in most patients • The average effective half - life was 24.1 hours (calculated from the extent of accumulation)
BLU - 945 treatment led to dose - dependent reductions in ctDNA a P atient had two different DNA mutations in C797S. Note: reductions in individual variant allele fractions as shown; therefore, pa tients with multiple mutations may be represented on both plots. All T790M and C797S allele fractions with available baseline and C1D15 data are shown. Increases of greater than 100% were truncated at 10 0%. C, Cycle; ctDNA, circulating tumor DNA; D, day; F1LCDx, FoundationOne Liquid CDx assay; QD, once daily.1. Ku BM et al. Oncology. 2022; Epub ahead of print. PMID: 35196661; 2 Ma L et al . Front Oncol. 2021;11:643199; 3. Fernandes MGO et al. Cells. 2021;10:1912. As of the data cut - off (March 9, 2022), 33 patients have been treated with BLU - 945 at 25 – 400 mg once daily (QD) in the first 5 c ohorts. Not for promotional use. 16 83% OF EGFR - T790M VARIANT ALLELES REDUCED WITH TREATMENT 81% OF EGFR - C797S VARIANT ALLELES REDUCED WITH TREATMENT EGFR - T790M ctDNA levels EGFR - C797S ctDNA levels • In the 400 - mg cohort, all detectable T790M and C797S alleles showed reduction, including three that fell below the limit of dete ction (clearance)
BLU - 945 showed dose - dependent anti - tumor activity, with tumor shrinkage reported at doses ≥200 mg QD a Patients with measurable target lesions at baseline with post - baseline scans (investigator assessed); b Data cut off, March 9, 2022; CR, complete remission; EOT, end of treatment; PD, progressive disease; PR, partial remission; QD, once daily; SD, stable disease. An unconfirmed PR is a PR in which tumor reduction ≥30% has occurred but has not yet been confirmed via a subsequent scan. As of the data cut - off (March 9, 2022), 33 patients have been treated with BLU - 945 at 25 – 400 mg once daily (QD) in the first 5 cohorts . 17 Not for promotional use. • Unconfirmed PR reported in patient with ex19del/T790M/C797S treated at 400 mg QD • Dose escalation from 100 to 200 mg QD led to stabilization of tumor growth in two patients
Patient 2 • 70 - year - old Asian female, no smoking history • Diagnosed stage IVB • Three prior therapies, achieved PRs and PD • Multiple target and non - target lesions • 200 mg QD • All detectable mutations decreased at C1D15 • 21% and 28% tumor reduction at C2D1 and C3D1, respectively Patient cases: BLU - 945 demonstrated encouraging signs of clinical activity in patients treated at higher doses QD, once daily. SD, stable disease. PR, partial response. PD, progressive disease. An unconfirmed PR is a PR in which tumor reduction ≥30% has occurred but has not yet been confirmed via a subsequent scan. As of the data cut - off (March 9, 2022), 33 patients have been treated with BLU - 945 at 25 – 400 mg once daily (Q D) in the first 5 cohorts. Not for promotional use. Patient 1 • 69 - year - old Caucasian female, no smoking history • Diagnosed stage IV NSCLC • Three prior therapies with best response of SD • Multiple target and non - target lesions, including non - target in brain • 400 mg QD • All detectable mutations decreased at C1D15, with C797S clearance • Unconfirmed PR; 30% tumor reduction at C2D1 18
Patient case: ctDNA and exposure analyses in patient treated at 50 mg highlight polyclonal disease and potential of combination treatment QD, once daily. EOT, end of treatment. I/O, immunotherapy. As of the data cut - off (March 9, 2022), 33 patients have been treated with BLU - 945 at 25 – 400 mg once daily (QD) in the first 5 cohorts. • 57 - year - old Asian female • Several prior therapies (multiple TKIs, chemo, I/O) • No brain metastases at screening • Treated with BLU - 945 at 50 mg QD • EOT at C2D1 due worsening pleural effusion • Divergence in mutation allele fractions suggest polyclonal disease with some tumors harboring ex19del alone • Combination therapy and/or increasing BLU - 945 exposure at higher doses may hold promise for treating late - line polyclonal disease 19 Not for promotional use.
Conclusions • In the ongoing Phase 1 trial, BLU - 945, a highly potent and selective oral EGFR inhibitor, was generally well tolerated at clinically active doses in heavily pre - treated patients with EGFRm NSCLC • Few AEs characteristic of wild - type EGFR toxicity observed at doses up to 400 mg QD • Despite presence of EGFR mutations conferring resistance to osimertinib, treatment with BLU - 945 resulted in rapid dose - dependent reductions in ctDNA, consistent with preclinical data • Increasing BLU - 945 doses were associated with increasing antitumor activity, with tumor shrinkage noted at doses of 200 mg QD and above, including an unconfirmed partial response at 400 mg QD • The clonal evolution and resulting mutational complexity of EGFR - driven NSCLC tumor cells demonstrates the need for precision medicine combinations to improve clinical outcomes • Initial safety and clinical activity results support expanded clinical development of BLU - 945 in combination with osimertinib and other complementary agents 20 Not for promotional use. AE, adverse event. QD, once daily. ctDNA, circulating tumor DNA. An unconfirmed PR is a PR in which tumor reduction ≥30% has occ urred but has not yet been confirmed via a subsequent scan. As of the data cut - off (March 9, 2022), 33 patients have been treated with BLU - 945 at 25 – 400 mg once daily (QD) in the first 5 cohorts.
Acknowledgements 21 • Participating patients and families • SYMPHONY trial investigators and research coordinators • Clinical trial sites: • Colleagues at Blueprint Medicines Corporation Cedars - Sinai Medical Center, Los Angeles, CA Samsung Medical Center, Seoul, Korea Dana - Farber Cancer Institute, Boston, MA Sarah Cannon Research Institute, Nashville, TN Kanagawa Cancer Center, Yokohama - shi, Kanagawa, Japan Seoul National University, Department of Internal Medicine, Seoul, Korea Massachusetts General Hospital, Boston, MA The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK National Cancer Centre Singapore, Singapore The University of Texas MD Anderson Cancer Center, Houston, TX National Cancer Center Hospital, Chuo Ku, Tokyo, Japan UC Irvine Health, Chao Family Comprehensive Cancer Center, Orange, CA National Cancer Center Hospital East, Kashiwa, Chiba, Japan University of Colorado Hospital - Anschutz Cancer Pavilion (ACP), Aurora, CA National Taiwan University Hospital, Taipei, Taiwan Vall d'Hebron University Hospital, Oncology Department, Barcelona, Spain NYU Langone Health, Laura and Isaac Perlmutter Cancer Center, New York, NY Yonsei Cancer Center, Severance Hospital, Yonsei University, Seoul, Korea Not for promotional use.
Portfolio strategy and next steps Fouad Namouni, MD, President, R&D
Early BLU - 945 dose escalation data achieve clinical proof - of - concept 23 Dose - dependent reductions in ctDNA allele fractions for EGFR resistance mutations targeted by BLU - 945 Increasing coverage of EGFR activating and resistance mutations at higher doses, based on pharmacokinetic data Generally well - tolerated, with no significant adverse events associated with wild - type EGFR inhibition Dose - dependent antitumor activity, with reductions in target lesions observed at 200 mg QD and higher DATA SUPPORT INITIATION OF BROAD COMBINATION DEVELOPMENT STRATEG Y Not for promotional use.
Phase 1/2 trials to rapidly generate data in broad populations, informing development and registration strategies PLANNED INITIATION OF PHASE 1/2 SYMPHONY / HARMONY TRIAL COHORTS 1L 2L+ 2023 701 + ADC 945 + osi 701 + chemo 701 + osi Q2 2022 945 + osi 945 2H 2022 945 + ADC 701 945 + 701 945 + chemo 701 + osi Biomarker - selected Broad populations 24 945 + 701 Not for promotional use.
Phase 1/2 VELA trial of BLU - 222 advancing toward clinical proof - of - concept CCNE1, cyclin E; CDK4/6i, CDK4/6 inhibitor; ER, estrogen receptor. 25 Multiple dose cohorts* RP2D Combo with ER antagonist – ER+/HER2 - breast Combo with CDK4/6i + ER antagonist – ER+/HER2 - breast Monotherapy – CCNE1 tumors PHASE 2 EXPANSION (PLANNED) PHASE 1 DOSE ESCALATION (NOW ENROLLING) Combo with chemotherapy – CCNE1 tumors PHASE 1/2 VELA TRIAL OF BLU - 222 INITIATED IN Q1 2022 AND FIRST P ATIENT DOSED • Safety • Preliminary clinical activity • Patient selection strategy PHASE 1/2 TRIAL OF BLU - 222 IN CDK2 VULNERABLE CANCERS Not for promotional use. *Includes monotherapy and combination regimens Monotherapy – multiple other CCNE1 tumors (basket cohort)
Significant progress across our portfolio will drive near - term news flow 26 Top - line PIONEER trial data in non - advanced SM with potential to significantly expand AYVAKIT label Multiple anticipated datasets for EGFR and CDK2 programs with potential to unlock broad patient opportunities Plan to unveil new research programs and vision for scientific platform expansion at R&D Day Not for promotional use. MID - 2022 2H 2022 THRU 2023 2H 2022
Thank You
Exhibit 99.2
 |
Blueprint Medicines Announces BLU-945 Proof-of-Concept Data Supporting Initiation of Comprehensive Combination Development Strategy in EGFR-mutant Non-Small Cell Lung Cancer
-- Early dose escalation data show dose-dependent reductions in ctDNA and tumor burden --
-- Generally well-tolerated with most AEs Grade 1 or 2, supporting continued dose escalation --
-- Initiating SYMPHONY trial cohort to evaluate BLU-945 in combination with osimertinib --
-- Clinical trial supply agreement signed with AstraZeneca to provide osimertinib for combination development in ongoing BLU-945 and BLU-701 trials --
-- Blueprint Medicines to host investor conference call and webcast on Friday, April 8 at 2:00 pm ET --
CAMBRIDGE, Mass., April 8, 2022 -- Blueprint Medicines Corporation (NASDAQ: BPMC) today announced proof-of-concept data from the Phase 1/2 SYMPHONY clinical trial of BLU-945, an investigational precision therapy for advanced EGFR-mutant non-small cell lung cancer (NSCLC). The trial results showed early evidence of safety and clinical activity consistent with preclinical data, supporting plans to expand development of BLU-945 in combination with multiple agents including osimertinib, with the goal of preventing or treating tumor resistance to prolong patient benefit. The data were reported today at the American Association for Cancer Research (AACR) Annual Meeting 2022 in New Orleans.
Early data from the ongoing Phase 1 dose escalation part of the SYMPHONY trial showed dose-dependent decreases in circulating tumor DNA (EGFR variant allele fractions) and radiographic tumor reductions, including a partial response (PR) in a patient treated with 400 mg once daily (QD), the highest dose tested as of the data cutoff date. Pharmacokinetic results showed BLU-945 exposures at higher doses were associated with broad EGFR mutation coverage, including the activating L858R mutation with or without the osimertinib-resistant C797S mutation. BLU-945 was generally well-tolerated, with no significant adverse events (AEs) associated with wild-type EGFR inhibition. The maximum tolerated dose and recommended Phase 2 dose have not yet been identified, and dose escalation is continuing.
“Today, targeted therapies are the mainstay treatment for EGFR-mutant lung cancer, but tumor resistance emerges in the majority of patients, driving mutational heterogeneity and disease progression. Innovative treatment strategies, including targeted therapy combinations, are urgently needed to prevent or treat this mutational heterogeneity and prolong patient benefit,” said Elaine Shum, M.D., assistant professor in the Department of Medicine and a medical oncologist at NYU Langone Health’s Perlmutter Cancer Center, and an investigator on the SYMPHONY trial. “The initial BLU-945 data reported today, which highlight its potential to address resistance to current standard of care therapies including osimertinib and enable well-tolerated, broad-acting combinations, are an important step forward toward improving outcomes for patients with EGFR-mutant lung cancer.”
“We believe BLU-945 is distinguished from other EGFR-directed therapies, based on its ability to inhibit the most difficult-to-target EGFR mutations while maintaining a wide therapeutic index over wild-type EGFR, a known driver of toxicity. As a result, BLU-945 has significant potential as a combination partner with other targeted therapies and broad-acting agents,” said Fouad Namouni, M.D., President, Research & Development at Blueprint Medicines. “We are excited to see the preclinical profile of BLU-945 translated in the clinic, with early dose escalation data showing evidence of clinical activity, broad EGFR mutation coverage and tolerability. Based on these promising data, we plan to rapidly expand development of BLU-945 in combination with osimertinib and other agents to address important medical needs across all lines of therapy.”
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Blueprint Medicines is initiating a SYMPHONY trial cohort assessing BLU-945 in combination with osimertinib in patients with second-line or later EGFR-mutant NSCLC, following disease progression on osimertinib. After the selection of a recommended Phase 2 combination dose regimen, the company plans to initiate an expansion cohort with registration potential in biomarker-selected second-line patients, as well as an expansion cohort in front-line patients, by the end of 2022. Additional combinations with BLU-701, chemotherapy and antibody-drug conjugate therapy are planned across multiple mutation profiles and lines of therapy.
In addition, Blueprint Medicines announced today a clinical trial supply agreement with AstraZeneca (LSE/STO/Nasdaq: AZN). Under the terms of the agreement, Blueprint Medicines will evaluate BLU-945 and BLU-701 in combination with osimertinib in the ongoing SYMPHONY and HARMONY trials, respectively.
BLU-945: Data from the Phase 1/2 SYMPHONY Trial
As of a data cutoff date of March 9, 2022, 33 patients with EGFR-mutant NSCLC have been treated with BLU-945 across five dose escalation cohorts (range: 25-400 mg QD). The majority of patients (79 percent) previously received at least three lines of systemic therapy, including osimertinib (97 percent). Patient eligibility criteria require the presence of an EGFR mutation based on local assessment of tumor biopsy or circulating tumor DNA (ctDNA).
BLU-945 was generally well-tolerated at all doses tested. The most common AEs (regardless of relationship to BLU-945; ≥10 percent) were nausea, headache, fatigue, cough, dyspnea, vomiting, hyponatremia, dry mouth and anemia. Reported AEs associated with wild-type EGFR inhibition were infrequent and low grade, including rash (one patient; Grade 1) and diarrhea (three patients; all Grade 1). One dose-limiting toxicity (Grade 3 transaminitis) occurred in the 400 mg QD cohort, which improved with dose interruption. There were no treatment discontinuations due to AEs.
Pharmacokinetic data showed dose-proportional plasma concentrations, with exposures at increasing doses consistent with broad EGFR mutation coverage, based on preclinical activity thresholds. Mean plasma exposures at doses of 100 mg QD or higher exceeded the IC90 for mutants harboring the T790M and C797S resistance mutations, regardless of activating mutation. In addition, mean plasma exposure at 400 mg QD exceeded the IC90 for mutants harboring the activating L858R mutation with or without the C797S mutation.
The SYMPHONY trial is one of the first oncology studies to analyze plasma ctDNA via real-time next-generation sequencing to assess tumor biology and early drug activity. Results for patients with detectable T790M and C797S allele fractions at baseline and available post-baseline assessments showed dose-dependent reductions in both variant allele fractions. In patients treated with 400 mg QD, all detectable T790M and C797S allele fractions declined, including three that fell below the limit of detection (clearance).
Patients with measurable target lesions at baseline and at least one post-baseline scan were evaluable per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. In a heavily pre-treated population, higher BLU-945 doses led to increased antitumor activity. Tumor shrinkage was observed in patients treated with 200-400 mg QD, including an unconfirmed PR1 in a patient treated with 400 mg QD. This patient had NSCLC harboring exon 19 deletion, T790M and C797S mutations, and previously received platinum-based chemotherapy, erlotinib and osimertinib with a best response of stable disease.
1 An unconfirmed PR is a PR in which tumor reduction ≥30% has occurred, but has not yet been confirmed via a subsequent scan.
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Copies of Blueprint Medicines data presentations from the AACR annual meeting, including the SYMPHONY trial presentation, are available in the “Science—Publications and Presentations” section of the company’s website at www.blueprintmedicines.com.
Investor Conference Call Information
Blueprint Medicines will host a live webcast today, April 8, 2022 beginning at 2:00 p.m. ET, to discuss the data reported at AACR. To access the live call, please dial 844-200-6205 (domestic) or 929-526-1599 (international), and refer to conference ID 084402. A webcast of the conference call will be available in the Investors & Media section of Blueprint Medicines’ website at http://ir.blueprintmedicines.com/. 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.
About Blueprint Medicines’ Clinical Development Programs in EGFR-Mutant NSCLC
Blueprint Medicines is developing three investigational agents, BLU-701, BLU-945 and BLU-451, with the goal of addressing nearly all activating mutations (>90 percent) in EGFR-mutant NSCLC. The introduction of EGFR-targeted therapies, including osimertinib, has transformed the care of patients with EGFR-mutant NSCLC; however, there is a significant need for new treatment options designed to prevent or treat a broad range of resistance mechanisms before they emerge, with the goal of prolonging patient benefit. There are no approved targeted therapies for patients with disease progression following osimertinib, and limited treatment options for patients with EGFR exon 20 insertion-positive NSCLC.
BLU-701 and BLU-945 were designed to provide broad coverage of common activating and on-target resistance mutations, spare wild-type EGFR and other kinases to help limit off-target toxicities, and prevent or treat central nervous system (CNS) metastases. These preclinical profiles may enable BLU-701 and BLU-945 to become the backbones of a range of combination strategies across lines of therapy. The Phase 1/2 SYMPHONY trial (NCT04862780) of BLU-945 and the Phase 1/2 HARMONY trial (NCT05153408) of BLU-701 are currently ongoing for patients with EGFR-mutant NSCLC.
BLU-451 is a selective and potent inhibitor of EGFR exon 20 insertion-positive NSCLC. Based on preclinical data, BLU-451 potently inhibited all common EGFR exon 20 insertion variants with marked selectivity over wild-type EGFR and off-target kinases, and has shown CNS penetration. Blueprint Medicines has initiated a Phase 1/2 trial of BLU-451 (NCT05241873) in EGFR exon 20 insertion-positive NSCLC.
To learn about ongoing or planned clinical trials, contact Blueprint Medicines at medinfo@blueprintmedicines.com or 1-888-BLU-PRNT (1-888-258-7768). Additional information is available at blueprintclinicaltrials.com or clinicaltrials.gov.
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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 Blueprint Medicines’ plans, strategies, timelines and expectations for clinical trials, trial cohorts and indications; the anticipated benefits of the preclinical profiles of BLU-945, BLU-701 and BLU-451; Blueprint Medicines’ plans, strategies and timelines for the development of BLU-945 and BLU-701 as monotherapies and in combination with other agents; the potential benefits of Blueprint Medicines’ current or future approved drugs or drug candidates in treating patients; and Blueprint Medicines’ 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 establishing a commercial infrastructure, and successfully launching, marketing and selling current or future approved products, including AYVAKIT® (avapritinib) and GAVRETO® (pralsetinib); Blueprint Medicines’ ability to successfully expand the approved indications for AYVAKIT and GAVRETO or obtain marketing and reimbursement approvals for AYVAKIT and GAVRETO 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 and marketing applications; Blueprint Medicines’ ability to develop and commercialize companion diagnostic tests for 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; Blueprint Medicines’ ability to realize the anticipated benefits of its executive leadership transition plan; and the success of Blueprint Medicines’ current and future acquisitions, collaborations, 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.
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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 approved medicines directly to patients in the United States and Europe, and we are globally advancing multiple programs for systemic mastocytosis, lung cancer and other genomically defined cancers, and cancer immunotherapy. For more information, visit www.BlueprintMedicines.com and follow us on Twitter (@BlueprintMeds) and LinkedIn.
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