QD, once daily; RECIST v1.1, RECIST daily; onceQD, NSCLC, non ( rate control BICR, blinded central independent review; CBR, clinical benefit rate ( a • • • • • investigator’sdecision (n=3), and administrative reason/other (n=2). measurable disease confirmed on blinded central independent review. 400 mg QD pralsetinib with any tumor type. tumor any with pralsetinib QD mg 400 a Results Patients with medullary thyroid cancer did not require documented Includes all patients enrolled by May 22, 2020 (enrollment cutbyenrolled Mayallpatients 2020(enrollment 22, Includes • • • • • Eligibility criteria of Ulsaarn College of , Seoul, Republic ofKorea; 18 13 Giuseppe Curigliano, non-small cell lungcancer: update fromthe ARROW trial Safety and efficacy ofpralsetinib inpatients withadvanced Luis Paz (TLRC-H), Member ofthe German Center forLung Research (DZL)Heidelberg, Germany; 1 M Patient disposition/analysispopulations ARROW studydesign Background andmethods NSCLC enrolled in ARROW were presented at at in 2020 presented were enrolled ASCO NSCLC ARROW per comorbidities, or other poor prognostic factors prognostic poor other or comorbidities, In this update we provide longer follow longer we provide update this In – Initially, treatment all advanced with patients for dataset registrational the from Findings RET with RET inhibitor, in patients selective oral, potent, a highly pralsetinib, FDA of supported approval (NCT03037385) study ARROW registrational 1/2 phase The ( during transfection Rearranged fusion non European Institute of Oncology, IRCCSand University ofMilano, Milan, Italy; treatment ECOG PS 0 ECOG (RECIST v1.1) disease Measurable assessment RET tumor solid metastatic or Advanced years ≥18 Age platinum Mayo Clinic, Rochester, Minnesota, USA; Institut Universitairedu Cancer, Toulouse, France; RET RET easurable disease population disease easurable with with RET Protocol amendment 115 discontinued treatment 115 discontinued Eligibility criteria were provide a study population more representative of the real the of representative more population a study provide of treatment of enrollm allowing 2019, in July amendment a protocol by expanded were criteria Eligibility - - 101 continuing treatment 101 continuing protocol to not be candidates for standard platinum standard for be candidates not to protocol expanded to allow small cell lung cancer (NSCLC) lung cancer cell small fusion 30 adverse event event 30 adverse progression 70 disease 15 other - (July 19 confirmed CR or PR or SD); DOR, duration of response; ECOG PS, Eastern PS, ECOG response;of duration DOR, SD); or PR or CR confirmed alteration per local local per alteration Patients who received pralsetinib at the RP2D at RP2D the of 400 mg QD pralsetinib who received Patients – small cell lung cancer; ORR, overall response rate; OS, overall surviva candidates for NSCLC whoNSCLC positive NSCLC enrolled in the ARROW study before and after the eligibility revi eligibility the and after before in the study enrolled NSCLC ARROW positive fusion 14 treatment fusion - – - based therapy positive NSCLC and advanced/metastatic and advanced/metastatic NSCLC positive naïve patients –1 - naïve patients who patients naïve , – – n=216 c n=233 2019) Response Evaluation CriteriaEvaluation inResponse Solid Tumors version1.1; RET, durrearranged positive NSCLC positive - - Ares, naïve patients with advanced advanced with patients naïve wer - related related e b Subset of patients in the efficacy population with sufficient evidence of a Safetypopulation, N=471 NSCLC RET 12 were Phase 2 dose determined: 1–4 Phasedose 1 escalation ) RET - Other fusions are targetable oncogenic drivers 1 in drivers oncogenic targetable are fusions Julien Mazieres, up with a focus on treatment a focus with up Medullary thyroid - off) in dose escalation (phase 1) and dose expansion (phase 2) wh (phase expansiondose 1) and (phase escalation indose off) candidates for platinum for standard candidates b (Completed) RET 400 mg QD mg 400 RP2D, recommended phase 2 dose. phase recommended RP2D, fusion CR or PR or SD of ≥16 weeks); CR, complete response; complete CR, weeks); ≥16 of SD or PR or CR NSCLC cancer c tumors Other reasons for were discontinuation withdrawn consent (n=10), RET mutations for enrollment.for mutations 1 – RET RET - Other Other Justin F. Gainor, March March 17, 2017, and May 22, 2020 altered positive positive a Median follow l; PFS, PFS, l; progression RET - based therapy, generally due to age, therapy, age, due to based generally Data presented for patients presented for Data fusion Cooperative Oncology Group performance status; performance Group Oncology Cooperative - 6 altered thyroid cancers thyroid altered RET - Data Data cut world population world November 6, 2020 enrolled between – positive NSCLC were required required were NSCLC positive a 19 - - RET RET Blueprint Corporation, Cambridge, Massachusetts, USA; Blueprint free survival; free PR, partial altered solid tumors solid altered • • • • • - Phasedose 2 expansion naïve patients with with patients naïve n=238 DCR CBR DOR Safety v1.1) RECIST ORR (BICR per Treated at 400 mg QD mg 400 at Treated Key Key - ing transfection; SD SD stabletransfection; ing disease - metastatic up: 17.1 months 17.1up: fusion off date of date off 1º - based therapy, based to 2º (Ongoing) endpoints: RET 13 14 – endpoints: positive positive fusion andfusion baseline Georgetown University,Washington, DC, USA; DCR, diseaseDCR, Stephen V. Liu, 5 – response; 2% of 2% of o received • • sion OS OS PFS RET 2 ent ent Frank Griesinger,Frank . ECOG ECOG PS, Eastern Cooperative Oncology Group performance status; PD permitted. not beenpreviously a CI, confidence interval;mDOR, median duration of response; mo, month; by May pralsetinib 2020. 22, permitted. not beenpreviously a 9 CBR, %(95% CI) DCR, %(95% CI) mDOR, mo (95% CI) (95% mo mDOR, (95% CI) % ORR, Best overallBest (%)response, n mPFS Protocol amendment July amendment Protocol thisinclusion 2019; criteriato expanded amendment allow Protocol amendment July amendment Protocol thisinclusion 2019; criteriato expanded amendment allow ECOG PS, n (%) n PS, ECOG Smoking , n (%) n history, Smoking Race, n (%)Race, n Male, n (%)Male, n Prior therapy type, n (%) type, therapy Prior Brain metastases, n (%) metastases, n Brain Median age (range), years (range),age Median Helios ClinicEmilvon Behring, , Germany; NE PD CR SD PR Tumor shrinkage inpatients with prior platinum-based chemotherapy Efficacysummary(blinded independent central review) characteristics Baseline 2 1 0 Never Current/former Other/unknown Asian White Multikinase inhibitor PD Platinum b

Maximum percent reduction from - (L)1 inhibitor (L)1 , mo

– baseline in target lesion diameter 100 – – – – - based (95% CI) 80 60 40 20 20 0 2 Massachusetts General Hospital, Boston, Massachusetts, USA; Massachusetts 14 b c Presented at at Presented d b b ECOG ECOG PS of 2 was priorpermitted to amendment inprotocol July 2018. Gregory Kalemkerian, Confirmed CR CR or PR or SD. Confirmed 16.4 (11.0 c fusion 22.3 (15.1 (62 92 (87 77 (71 3 6)5 7)2 6)2 8)7 5)16 (73) 73 (58) 22 (88) 28 (65) 50 (74) 139 (64) (n=216) NSCLC 50 (23) n=233 10 (5) 4 3 2 4 6(5) 1(4) 1(2) 2(3) 8 (4) 4 6 4(9) 4(6) 9 (4) RET 69 – fusion – positive positive 75) – – – 95) 82) 3 – 113 (52) 5 137 (63) 133 (62) 104 (48) 126 (58) 126 (58) (n=216) NSCLC (26 24.1) NR) 73 (34) 80 (37) 20 (9) 83 (38) 40 (19) 82 (38) 66 (31) University of Texas MD Anderson Cancer Center, Houston, Texas, USA; RET 3 1 1(2) 1(1) 6 (3) – 60 – Michael Thomas, positive positive 87) ASCO 2021, 13.0 (9.1 c NR (9.0 CR or PR or SD of ≥16 weeks. ≥16 of SD or PR CR or (68 93 (84 82 (71 (n=68) 1)7(6 2(8) 7(16) 9 (13) n=75 4 3(7) 3 (4) 79 All – 88) – – – – 98) 91) NR) 15 - NR) mPFS (30 (L)1, programmed cell death/programmed cell death ligandcell death celldeath/programmed (L)1, programmed 8(6 4(6 14(56) 24(56) 38 (56) 9(3 8(2 11(44) 18(42) 29 (43) 6(3 2(1 14(56) 22(51) 36 (53) 1(6 0(7 1(4 45(36) 11(44) 20(47) 31 (46) 14 (21) 8(1 7(3 1(4 1(0 14(64) 51(40) 21(84) 27(63) 48 (71) 5(1 4(6 1(4 2(9 7(32) 62(49) 11(44) 24(56) 35 (51) 2(2 5(5 7(28) 15(35) 22 (32) (n=68) 6 (9) All University of Michigan, Ann Arbor, Michigan, USA 61 0 0 – 0 87) , median progression median, Treatment Measurabledisease population recruitment of of recruitmenttreatment recruitment of of recruitmenttreatment 10.9 (7.7 11.0 (7.4 June 4 4 June Pre (59 91 (78 79 (64 revision (n=43) Measurable disease population disease Measurable - Treatment n=47 eligibility d 74 Evaluated Pre – 87) – – revision – – - (n=43) (30 97) 90) - 2(8 2(8) 12 (28) naïve a NR) NR) eligibility 20 9 2(8) 4 (9) - 65 free survival;free NE, not evaluable; NR, not reached; PD, progressivedisease. – 0 – 0 0 and University Medical Center Groningen, Groningen, in all patients with with patients in all 87) c History of or current. or of History - June 8, 2021, Virtual 2021, 8, June Format. a naïve 15 - - naïve patientsnaïve eligible for standard platinum naïve patientsnaïve eligible for standard platinum Post eligibility NR (NR NR (NR 10 4 (69 96 (80 88 (69 revision Vall d’HebronInstitute ofOncology (VHIO),Barcelona, Spain; (n=25) Yariv Houvras, n=28 Post eligibility Vivek Subbiah, 88 – 0 0 revision 98) – – RET RET (n=25 (35 – – 100) 98) NR) NR) a 54 0 – 0 0 0 fusion 80) ) a - – 1. 16.5 (10.5 positive NSCLC who initiated 400 mg QD QD mg 400 initiated who NSCLC positive 22.3 (15.1 (53 91 (85 74 (65 platinum (n=126) ` 37 (29) n=136 Prior Prior 4 2(9) 5 (4) 5 (4) 62 platinum 126 (100) (n=126) – (26 4(7 10(45) 34 (27) 79 (63) 79 (63) 4(1 5(23) 64 (51) 2(1 14(64) 6(27) 52 (41) 34 (27) 2(1 8(36) 52 (41) 7(9 12(55) 87 (69) 11 (9) 3 (14) 3(14) 11 (9) Prior Prior 5 (4) 70) – – Prior treatment Prior 60 – – 96) 81) – 24.1) 85) Prior treatment Prior NR) - - based therapybased who had based therapybased who had 12.8 (9.1 non NR (9.2 non (50 91 (71 77 (55 (n=22) (47 4 (18) 3 - (n=22) Prior n=22 16 - platinum 18 (82) Prior 73 Pius-Hospital, University ofOldenburg, platinum 4 (18) – 5 0 0 61 – – 20% 0 0 – 89) – – 84) 30% 100% – Please contact [email protected] for permission to reprint and/orPlease distribute contact [email protected] – 99) 92) NR) Christina S. Baik, NR) Daniel W. Bowles,

; 16 previously not been permitted. permitted. not beenpreviously a Number at risk at Number previously not been permitted. permitted. not beenpreviously a Protocol amendment July amendment Protocol thisinclusion 2019; criteriato expanded amendment allow Protocol amendment July amendment Protocol thisinclusion 2019; criteriato expanded amendment allow Weill Cornell Medical College University,New York, New York, USA; Prior platinum Prior revision Pre revision Post eligibility Number at risk Maximum percent reduction from treatment No priorsystemic Duration of response in patients with Duration ofresponse inpatients with prior platinum Duration ofresponse intreatment-naïve patients Tumorshrinkage intreatment-naïve patients

– baseline in target lesion diameter - eligibility eligibility – – – – 100 20 80 60 40 20 a a Duration of response (%) Duration of response (%) 0 6 University of Washington School of Medicine, Seattle, Washington, USA; 100 100 80 40 60 20 40 60 80 20 0 0 874 78 0 45 014 30 50 54 221 22 22 114 21 29 32 0 Censored revision eligibility post Enrolled Enrolled pre Enrolled treatment systemic prior No 6 9 3 17 3 Daniel SW Tan,Daniel Prior platinum Censored Aaron S. Mansfield,Aaron Months from first documentedfirst responseMonths from (CR/PR) Months from first documentedfirst responseMonths from (CR/PR) - eligibility revision 6 11 57 44 6 Enrolled post eligibility revision eligibility post Enrolled Enrolled pre Enrolled 0 9 , Germany; Germany; Oldenburg, Seoul National University Hospital, Seoul, Republic of Korea; - based chemotherapy 9 - eligibility revision RET recruitment of of recruitmenttreatment recruitment of of recruitmenttreatment 12 53 20 31 35 12 0 1 1 4 7 0 1 1 4 7 7 Dae Ho Lee, a 15 - a naïve patientsnaïve eligible for standard platinum - naïve patientsnaïve eligible for standard platinum 15 4 Thoracic Oncology, Thoraxklinik, University Heidelberg and Translational Lung Research Center Heidelberg fusion–positive 18 18 - based chemotherapy 18 Alena Zalutskaya, 21 0 2 9 21 8 - based therapybased who had - based therapybased who had 17 Daniel Misch, Daniel 24 University of Colorado School of Medicine, University Aurora, Colorado, USA; 24 – – 20% 27 100% 30% 7 National Cancer Centre Singapore, Singapore; Singapore, Centre Cancer National Samsung. Travel, andAccommodations, Expenses: Pfizer, H Roche/Genentech. upon request at Novartis,Samsung, and Pfizer, Seattle Roche/Genentech, Genetics.Speakers B Dr. Giuseppe Curigliano has a consultingor advisory role with the followi Disclosures guidelines.Practice 7. CStone Pharmaceuticals Press Release. March 2021. 24, PressRelease. Pharmaceuticals 7. CStone https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/214701s000lbl. support was provided by Travis Taylor, BA, all of Paragon, Knutsford, UK, s The authorswouldlike to thankthe their patients,and families, all in Acknowledgements 2012;18:378 1. Mulligan LM. LM. Mulligan 1. References • • • AE, AE, adverse event; ALT, alanineAST, aminotransferase; aspartate aminotransfera a cut enrollment 2020, 22, May the onor before mg QD pralsetinib Treatment All patients (N=471) includes patients with other tumor types (inclu AST increased White blood cell count decreasedcellbloodWhite Asthenia yepopaei 11 Hyperphosphatemia Neutropenia Anemia Lymphopenia ALT increased Constipation Diarrhea Blood creatinineincreased Dry mouth Pneumonitis Hypertension Dysgeusia Blood creatine phosphokinase increased Thrombocytopenia Edema 19 Notably,ORR was88% inthe post eligibilityrevision subset, which • • Pralsetinib is currently approved for Pralsetinib is currentlyapproved for the treatment of metastatic • • Pralsetinib isawell- • • AE, % AE, Conclusions Treatment- to treatment A of 471 total26 of patients the (6%) in overall safety population (all tumor types) 72 (15%) and 64 (14%) patients (all tumor types), respectivelytumor types),patients (all (14%) and 64 (15%) 72 Only2 (<1%)patients discontinued treatment due treatmentto Treatment after platinum after included treatment included RET platinum RET decisions healthcare withmetastatic NSCLC prior totreatment initiation to inform optimal for testing biomarker earlyof importance the solidify data These care of standard with thyroidcancers in the USA, With follow overall longer a With signals safety new no and reports previous with consistent analysis), Anthonie J. van der Wekken der van J. Anthonie - related AEs of any grade reported in ≥10% of patients in either the eitherin patients of ≥10% in reported grade any of AEs related b b 12 – 9 381; 5. 5. 381; b Hospital Universitario 12 de Octubre, Madrid,Spain; Nat Rev Cancer. Cancer. Rev Nat [email protected] RET Elena Garralda, b fusion fusion b b b BlueprintMedicines Corporation. GAVRETO - related neutropenia leading to treatment interruption or dose reduction was reportedrelated neutropeniareductiontreatment interruption in was dose leading orto - - related AEs b based therapy,based support providing 6 fusion related adverse events adverse related pralsetinib showed robust, durable responses across all all across responses durable robust, showedpralsetinib – –positive NSCLC and advanced or metastatic 2014;14:173 positive NSCLC treatment groups treatment positive NSCLC - based chemotherapy in China in chemotherapybased – positive metastatic NSCLC, with a safety profile profile safetya with NSCLC, positive metastatic – 186; 2. Kohno T al.et Kohno2. 186; b - naïve naïve patients who were otherwise eligible for standard tolerated once tolerated https://www.cstonepharma.com/en/html/news/2566.html - off. ™ ding MTC MTC ding irrespective of mutation status) who received pr - vestigators involved ininvolved this vestigators study.Medicalwriting s 5 (pralsetinib). Prescribing information. 2020. up (17.1 months vs 8.8 months previous in months 8.8 vs months (17.1 up Nat Med. Med. Nat Any grade and in locally advanced or metastatic and in locallyadvanced or metastatic NSCLC RET ng: AstraZeneca, BMS, ng: AstraZeneca,BMS, Boehringer, Daiichi Sankyo, F 10 upported byupported Blueprint Medicines Corporation,Cambr pdf 39 22 019 40 20 42 81 513 35 13 38 30 51 612 26 12 25 25 16 15 13 13 27 24 16 15 15 15 14 RET RET fusion . Accessed April 6, 2021; 6. Gainor JF, et al. et JF, Gainor6. 2021; 6, April Accessed . 2012;18:375 onoraria: Ellipses Pharma. Research funding: Merck. ureau: Daiichi Sankyo,Medicine, FoundationLilly Dong se; MTC, MTC, se; medullary thyroid cancer. fusion - daily oral treatment option for patients patients for option treatment oral daily (n=233) – – positive NSCLC positive population(n=233) or positive the entire safety (N=471) population that recei – 377; 3. Lipson D D al.et Lipson3. 377; - Grade 8 Wan Kim, for for RETinhibitors as first- Asan Medical Center, 3 7 2 9 3 7 4 0 2 0 1 1 0 0 0 5 20 ≥3 - related neutropeniatumor types) (all Nat Med. Med. Nat . Accessed May 4, 2021. 4, May Accessed . upp ort was provided by Jeremy Kennard, PhD, andeditorialPhD, bywas provided Jeremy Kennard, ort J Clin Oncol. als 2012;18:382 oun Any grade etinib 400 mg QD. QD. mg 400 etinib idg dation Medicine, Lilly, GlaxoSmithKline, dation , N e, MA according to Good Publication Good to accordingMA e, ovartis, Pfizer, Roche/Genentech, and Roche/Genentech, Pfizer, ovartis, 39 32 25 811 18 15 14 28 26 16 15 13 14 14 17 11 Ful RET- 11 l disclosures for all authors are available 2020;38 (suppl2020;38 15):9515. – 384; 4. Takeuchi K K al.et Takeuchi4. 384; All patients (N=471) discontinued discontinued due Number b altered altered Grouped term. Poster Poster 9089 all patients patients all a Grade line line 0 3 3 8 3 4 0 2 0 0 0 6 1 1 Nat Med. Med. Nat ≥3 ved 400