Full Press Release Details
CI, confidence interval; HCC, hepatocellular carcinoma; IHC, immunohistochemistry; TKI, tyrosine kinase inhibitor. Data previously presented in September 2017 at European Society for Medical Oncology (ESMO) 2017 Congress. Data cutoff: August 18, 2017. ORR = 16% (6-31% 95% CI) Most AEs were Grade 1 or 2 Grade 3 AEs in 5 patients included anemia, diarrhea and AST/ALT elevation Maximum Reduction sum of diameter change from baseline, % FISH+ FISH+ FISH+ FISH+ PR PR PR PR CR FISH+ PR 100 90 80 70 60 50 40 30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 Updated Phase 1 results FGF19 IHC+ population Preliminary Phase 1 trial results expected in 1H 2018 for BLU-667, a highly selective inhibitor of RET fusions and mutations 23 Phase 1 clinical trial Status: recruiting Open-label dose escalation RET-altered NSCLC with prior TKI (n=~20) Other RET-altered solid tumors (n=~20) Part 1 ongoing RET-altered NSCLC with no prior TKI (n=~20) Part 2 planned Medullary thyroid cancer (n=~20) BLU-667 MTD or RP2D As of December 1, 2017 30 patients have been enrolled in dose escalation, with enrollment ongoing BLU-667 has been generally well-tolerated Majority of AEs reported by investigators were Grade 1 MTD and RP2D have not been identified Preliminary evidence of clinical activity observed in patients with NSCLC (including KIF5B and other RET fusions) and RET-altered MTC Planned next steps Present preliminary clinical data in 1H 2018 Initiate expansion portion of Phase 1 trial in 1H 2018 BLU-782 selected as development candidate for potential treatment of fibrodysplasia ossificans progressiva 24 Devastating, ultra-rare genetic disease caused by mutant ALK2 Characterized by abnormal transformation of skeletal muscle, ligaments and tendons into bone Progressive loss of mobility and respiratory function, with median age of death of ~40 years Differentiated approach targets underlying cause of disease Plan to initiate IND-enabling studies in 1H 2018 TUMOR-LIKE SWELLINGS MALFORMED BIG TOES EXTRASKELETAL BONE PROGRESSIVE INCAPACITATION Cash to fund operating expenses and capital expenditures into mid-2020* * Cash guidance gives effect to estimated net proceeds received upon closing of underwritten public offering on December 15, 2017 but excludes any potential option fees and milestone payments under the existing collaboration with Roche. 25 SHARES OUTSTANDING AS OF 9/30/17 39.2 million (basic) 42.5 million (fully diluted) CASH, CASH EQUIVALENTS AND INVESTMENTS AS OF 9/30/17 $390.7 million 4.3 million shares issued ~$325.5 million SHARES ISSUED ESTIMATED NET PROCEEDS DECEMBER 2017 PUBLIC OFFERING Full summary of expected 2018 milestones 26 Program Milestone Anticipated Timing avapritinib GIST Initiate Phase 3 trial in 3L GIST for avapritinib compared to regorafenib 1H 2018 Explore expedited clinical development pathways for KIT-driven GIST with regulatory authorities 1H 2018 Complete enrollment of registration-enabling trial in PDGFR -driven GIST Middle of 2018 Present updated Phase 1 data for PDGFR , 3L+ and 2L GIST patient populations 2018 avapritinib SM Define registration strategy in SM with global regulatory authorities 1H 2018 Initiate registration-enabling trial in advanced SM 1H 2018 Initiate dose escalation and proof-of-concept trial in indolent and smoldering SM 2H 2018 Present expansion data from ongoing Phase 1 trial in advanced SM 2018 BLU-554 HCC Initiate Phase 1 trial cohort in TKI-na ve HCC Q1 2018 Present updated expansion data from ongoing Phase 1 trial in advanced HCC 2H 2018 Present initial data from Phase 1 trial cohort in TKI-na ve HCC 2H 2018 BLU-667 RET Present data from ongoing Phase 1 trial in RET-altered NSCLC, MTC and other advanced solid tumors 1H 2018 Initiate expansion portion of the Phase 1 trial in RET-altered NSCLC, MTC and other advanced solid tumors 1H 2018 BLU-782 FOP Present preclinical data on ALK2 program 2018 Initiate IND-enabling studies 1H 2018 Corporate Explore potential strategic collaborations 2018 Nominate at least two additional discovery programs 2018 Thank you
Data cutoff: October 4, 2017. Key Next Steps Plan to engage global regulatory authorities on registration pathways in 1H 2018 Pending regulatory feedback, plan to initiate: Registration-enabling trial in patients with advanced SM in 1H 2018 Dose escalation and proof-of-concept trial in patients with indolent and smoldering SM in 2H 2018 Continue enrollment of Phase 1 trial throughout 2018 Favorable tolerability profile Strong clinical activity Input from SM experts on clinical strategies Feedback from global regulatory authorities Program Status Registration-enabling clinical trials 20 Growing portfolio of highly selective investigational kinase medicines 21 BLU-554 Hepatocellular carcinoma FGFR4 BLU-667 Non-small cell lung cancer Medullary thyroid cancer Other RET-altered solid tumors BLU-782 Fibrodysplasia ossificans progressiva RET ALK2 Significant opportunity for selective FGFR4 inhibition with BLU-554 in evolving hepatocellular carcinoma landscape 22 Potential future treatment paradigm nivolumab BLU-554 +/- immune checkpoint inhibitor Other TKIs FGFR4-driven HCC (~30% of patients) Planned next steps Initiate TKI-na ve cohort in ongoing Phase 1 trial in Q1 2018 Consider options for combo trial with checkpoint inhibitor *4 confirmed PR; 1 PR/1 CR unconfirmed.
Data previously presented in December 2017 at the ASH Annual Meeting. Data cutoff: October 4, 2017. 18 Safety results showed avapritinib was well-tolerated in patients with systemic mastocytosis Data previously presented in December 2017 at the ASH Annual Meeting. Data cutoff: October 4, 2017. Most adverse events (AEs) reported by investigators were Grade 1 or 2 The most common treatment-emergent AEs reported by investigators ( 20%) across all grades included periorbital edema (59%), fatigue (41%), peripheral edema (34%), nausea (28%), anemia (28%), thrombocytopenia (28%), abdominal pain, diarrhea, respiratory tract infection, dizziness and headache (22% each) Investigators reported treatment-related Grade 3 AEs in 16 patients (50%), with only one treatment-related AE occurring in more than 10% of patients (neutropenia, 13%) No patients discontinued treatment due to treatment-related AEs 19 A strong foundation for development of avapritinib in systemic mastocytosis Data previously presented in December 2017 at the ASH Annual Meeting.
Data cutoff: October 4, 2017. 17 Serum tryptase at baseline: median 124 g/L, range 14 to 1414 g/L All 32 patients achieved >50% reduction from baseline Bone marrow mast cell burden at baseline: median 20%, range 1.5 to 95% n=25 evaluable patients with baseline bone marrow mast cells 5% 15/25 (60%) patients achieved bone marrow CR All evaluable patients had decreases in serum tryptase, bone marrow mast cell burden and spleen volume Best response2 n (%) (confirmed and unconfirmed) ASM (n=7) SM-AHN3 (n=8) MCL (n=3) Overall (n=18) Overall response rate (CR + PR + CI) 6 (86) 5 (63) 2 (67) 13 (72) CR + PR 5 (71) 4 (50) 1 (33) 10 (56) Complete response (CR) 2 (29) 0 0 2 (11) Partial response (PR) 3 (43) 4 (50) 1 (33) 8 (44) Clinical improvement (CI) 1 (14) 1 (13) 1 (33) 3 (17) Stable disease (SD) 1 (14) 3 (38) 1 (33) 5 (28) Progressive disease (PD) 0 0 0 0 72% objective response rate and 100% disease control rate observed in patients with systemic mastocytosis per rigorous IWG-MRT-ECNM consensus criteria1 17 of 18 patients remain on treatment with median duration 9 months (range: 4 19) 1 Gotlib J et al Blood (2013) 121:2393. 2 Pending confirmation: ASM, 2 CR; SM-AHN, 3 PR. 3 Mastocytosis response.
Spectrum Cases2 Patient impact Indolent SM (ISM) Smoldering SM (SSM) ~90-95% of patients have KIT D816V mutation1 Highly selective inhibition of D816V mutant KIT with avapritinib has broad potential applications across all subtypes of SM Debilitating symptoms Increasing organ dysfunction and damage Decreased overall survival3 16 Consistent clinical activity in systemic mastocytosis across outcome measures regardless of dose, disease subtype, prior midostaurin or presence of additional mutations Data previously presented in December 2017 at the American Societyy of Hematology (ASH) Annual Meeting.
Data previously presented in November 2017 at the CTOS Annual Meeting. Data cutoff: October 11, 2017. Key Next Steps Complete enrollment of registration-enabling Phase 1 trial in PDGFR -driven GIST by mid-2018 Initiate Phase 3 trial versus regorafenib in 3L GIST in 1H 2018 Explore expedited clinical development pathways for 3L+ (KIT-driven) GIST with regulatory authorities Continue enrollment of Phase 1 trial cohorts in 3L+ and 2L GIST throughout 2018 Favorable tolerability profile Strong clinical activity across multiple genotypes Breakthrough Therapy Designation in PDGFR D842V-driven GIST NDA submission in PDGFR -driven GIST Program Status 15 Registration-enabling trials (ongoing or planned) SM with Associated Hematologic Neoplasm (SM-AHN) Aggressive SM (ASM) Mast Cell Leukemia (MCL) Advanced SM ~16,100 patients ~1,800 patients ~2,600 patients 1Garcia-Montero AC et al, 2006. 2Represents estimated prevalence regardless of alteration in major countries (US, EU5 and Japan). 3Based on published natural history data.
Data cutoff: October 11, 2017. Cognitive effects are an aggregated category of individual cognitive events, each of which was observed in fewer than 20% of patients. Most adverse events (AEs) were Grade 1 or 2 Across all grades, the most common AEs included nausea (56%), fatigue (53%), periorbital edema (43%), vomiting (41%), peripheral edema (34%), anemia (31%), diarrhea (31%), increased lacrimation (30%), cognitive effects (30%), decreased appetite (28%), dizziness (23%), constipation (22%), and hair color changes (22%) Investigators reported treatment-related Grade 3 AEs in 39 patients (34%), including anemia (9%), fatigue (7%), hypophosphatemia (4%), nausea (4%) and cognitive effects (3%) Six patients (5%) discontinued treatment with avapritinib due to AEs 13 Ongoing and planned avapritinib clinical trials in patients with GIST 14 Key Part 2 goals: safety, ORR, duration of response Key goals: PFS, ORR, safety Phase 1 clinical trial Status: recruiting Phase 3 clinical trial Status: plan to initiate in 1H 2018 Open-label dose escalation (3+3) PDGFR D842V (n=50) 2L GIST (n=50) Part 1 complete 3L+ GIST (n=100) avapritinib RP2D Part 2 ongoing avapritinib (n=230) regorafenib (n=230) 3L GIST: randomized, double-blind Avapritinib clinical development program in GIST is rapidly advancing NDA, new drug application.
Clin Cancer Res. 2012;18(16):4458 64. 2 Yoo et al. Cancer Res Treat. 2016;48(2):546 52 CR, complete response. Data previously presented in November 2017 at the CTOS Annual Meeting. Data cutoff: October 11, 2017. 12 Maximum reduction: sum of diameter change from baseline (%) 71% objective response rate Best response (N=31)* RECIST 1.1 n (%) CR 1 (3) PR 21 (68) CR+PR 22 (71) SD 9 (29) DCR (CR+PR+SD) 31 (100) PD 0 *All dose levels included PR from C3 to C13, CR at C16, CR pending confirmation 3 pending confirmation Probability of progression-free survival (%) Approved agents are ineffective1,2 median PFS ~3 months Months from first dose Median PFS not reached; PFS at 12 months 78% Safety results showed avapritinib was well-tolerated in patients with GIST Data previously presented in November 2017 at the CTOS Annual Meeting.
Lancet Oncol. 2013;14(12):1175 82. DCR, disease control rate; MTD, maximum tolerated dose; PD, progressive disease; PR, partial response; RP2D, recommended part 2 dose; SD, stable disease. Data previously presented in November 2017 at the Connective Tissue Oncology Society (CTOS) Annual Meeting. Data cutoff: October 11, 2017. 11 Maximum reduction: sum of diameter change from baseline (%) Best response (N=30)* RECIST 1.1 n (%) PR 5 (17) SD 18 (60) DCR (PR+SD) 23 (77) PD 7 (23) Probability of progression-free survival (%) Months from first dose Imatinib re-treatment median PFS ~1.8 months2 Median PFS 11.5 months; PFS at 6 months 69% 67% of patients with tumor shrinkage *300 RP2D 400 MTD mg 2 pending confirmation Remarkable activity in PDGFR D842-mutant GIST via central radiology review 1 Cassier et al.
Roche has worldwide commercialization rights for up to three programs and ex-U.S. commercialization rights for up to two programs. 7 DRUG CANDIDATE (TARGET) DISCOVERY PRECLINICAL PHASE 1-2 PIVOTAL COMMERCIAL RIGHTS avapritinib (KIT & PDGFR ) BLU-554 (FGFR4) BLU-667 (RET) BLU-782 (ALK2) 2 undisclosed kinase targets Immunokinase targets Phase 1 Advanced PDGFR -driven GIST Phase 3 Advanced 3L GIST (planned 1H 2018) Phase 1 Advanced 3L+ (KIT-driven) GIST Phase 2 Advanced systemic mastocytosis (planned 1H 2018) Phase 1 Advanced systemic mastocytosis Phase 2 Indolent and smoldering systemic mastocytosis (planned 2H 2018) Phase 1 Advanced hepatocellular carcinoma Phase 1 Advanced NSCLC, thyroid and other cancers1 Fibrodysplasia ossificans progressiva Up to 5 cancer immunotherapy programs; development stage undisclosed2 2018 key priorities and expected milestones GIST, gastrointestinal stromal tumors. 8 avapritinib Portfolio Research Complete enrollment of registration-enabling trial in PDGFR -driven GIST by mid-2018 Initiate Phase 3 trial versus regorafenib in 3L GIST in 1H 2018 Initiate registration-enabling Phase 2 trial in advanced systemic mastocytosis in 1H 2018 Initiate Phase 2 trial in indolent and smoldering systemic mastocytosis in 2H 2018 Initiate TKI-na ve expansion cohort in Phase 1 trial of BLU-554 in hepatocellular carcinoma in 1Q 2018 Present dose escalation data and initiate expansion portion of Phase 1 trial of BLU-667 in RET-altered cancers in 1H 2018 Initiate IND-enabling studies for BLU-782 in fibrodysplasia ossificans progressiva in 1H 2018 Nominate at least 2 additional discovery programs in 2018 Avapritinib is a potential pipeline within a single investigational medicine SM, systemic mastocytosis. 9 KIT & PDGFR Gastrointestinal stromal tumors PDGFR -driven GIST 3L+ GIST 2L GIST Combination therapy Systemic mastocytosis Advanced SM Smoldering SM Indolent SM Other KIT & PDGFR -driven diseases Potent and selective KIT and PDGFR inhibition with avapritinib has the potential to address important medical needs in GIST ORR, objective response rate; PFS, progression free survival. * Imatinib re-challenged. ** Represents estimated incidence of GIST patients (regardless of alteration) and PDGFR D842V-driven GIST patients in major countries (US, EU5 and Japan). 3L+ GIST includes estimated incidence for 3L and 4L GIST. 10 Significant global opportunity PDGFR GIST 3L+ GIST 2L GIST ~500 patients ~7,500 patients ~7,700 patients Number of patients in major countries (US, EU5, Japan)** No highly effective therapies beyond imatinib 1L 2L 3L 4L imatinib sunitinib regorafenib No approved therapy ORR ~60% PFS 19 mo ORR ~7% PFS 6 mo ORR ~5% PFS 4.8 mo ORR ~0% PFS 1.8 mo* Approved agents are ineffective against PDGFR D842V GIST Tumor reduction and prolonged PFS observed in GIST patients with multiple KIT genotypes1 via central radiology review 1 KIT genotypes assessed by archival tumor and ctDNA.2 Kang et al.
(www.cellsignal.com) (CSTI). The foregoing website is maintained by CSTI, and Blueprint Medicines is not responsible for its content. 5 Genomic driver of disease Highly selective kinase medicine Selected patient population Achieve rapid clinical proof-of-concept Early go/no-go decisions Expedited development & regulatory approval Clear commercial value proposition TARGET OUTCOMES Realizing our vision for Blueprint Medicines * Includes up to 5 programs under the cancer immunotherapy collaboration with Roche. 6 2014 2015 STRATEGY LIBRARY TEAM 3 CLINICAL CANDIDATES WITH PROOF-OF-CONCEPT 2016 2017 CLINICAL CANDIDATES 4 TUMOR AGNOSTIC CLINICAL TRIALS 2 TUMOR TYPES & RARE DISEASES 6+ 2018 2019 Deliver transformational genomically targeted medicines to patients RESEARCH PROGRAMS* 8+ Robust pipeline of diverse clinical and preclinical stage assets NSCLC, non-small cell lung cancer. 1 Phase 1 trial includes a basket cohort that consists of other advanced solid tumors with RET alterations. 2 Blueprint Medicines has U.S. commercial rights for up to two programs.
The foregoing website is maintained by CSTI, and Blueprint Medicines is not responsible for its content. 4 Identify highly selective inhibitors of difficult to target disease drivers Eliminate inefficient drug discovery screening processes Accelerate time to development candidate selection Continuously enhance library to enable future discovery Proprietary library of compounds fully annotated against the human kinome BLU-554 Clinical strategy to rapidly bring transformative medicines to patients Kinome illustration reproduced courtesy of Cell Signaling Technology, Inc.
(www.cellsignal.com) (CSTI). The foregoing website is maintained by CSTI, and Blueprint Medicines is not responsible for its content. SELECTIVE AVAPRITINIB (FORMERLY BLU-285) NON-SELECTIVE MIDOSTAURIN SUNITINIB 3 Proprietary library rapidly delivers transformative medicines Kinome illustration reproduced courtesy of Cell Signaling Technology, Inc. (www.cellsignal.com) (CSTI).
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. 2 A new way of looking at kinase medicines Highly selective kinase medicines offer potential for improved potency, less off-target activity and increased probability of clinical success Kinome illustration reproduced courtesy of Cell Signaling Technology, Inc.
The Company cannot guarantee future results, outcomes, levels of activity, performance, developments, or achievements, and there can be no assurance that the Company's 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.
Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc. These and other risks and uncertainties are described in greater detail under Risk Factors in the Company's Quarterly Report on Form 10-Q for the quarter ended September 30, 2017, as filed with the Securities and Exchange Commission ( SEC ) on October 31, 2017, and any other filings the Company has made or may make with the SEC in the future.
These risks and uncertainties include, without limitation, risks and uncertainties related to the delay of any current or planned clinical trials or the development of the Company's drug candidates, including avapritinib, BLU-554, BLU-667 and BLU-782; the Company's advancement of multiple early-stage efforts; the Company's ability to successfully demonstrate the efficacy and safety of its drug candidates; the preclinical and clinical results for the Company's drug candidates, which may not support further development of such drug candidates; actions or decisions of regulatory agencies or authorities, which may affect the initiation, timing and progress of clinical trials; the Company's ability to obtain, maintain and enforce patent and other intellectual property protection for any drug candidates it is developing; the Company's ability to develop and commercialize companion diagnostic tests for its current and future drug candidates, including companion diagnostic tests for BLU-554 for FGFR4-driven HCC, avapritinib for PDGFR D842V-driven GIST and BLU-667 for RET-driven non-small cell lung cancer; and the success of the Company's cancer immunotherapy collaboration with F.
The Company has based these forward-looking statements on management's current expectations, assumptions, estimates and projections. 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.
In this presentation, forward-looking statements include, without limitation, statements about plans and timelines for the development of avapritinib (formerly known as BLU-285), BLU-554, BLU-667 and BLU-782 and the ability of Blueprint Medicines Corporation (the Company ) to implement those clinical development plans; the potential benefits of the Company's current and future drug candidates in treating patients; plans and timelines for regulatory submissions, filings or discussions; plans and timelines for the development and commercialization of companion diagnostics for the Company's current or future drug candidates; plans and timelines for current or future discovery programs; plans and timelines for any current or future collaborations with strategic partners; expectations regarding the Company's existing cash, cash equivalents and investments or the future financial performance of the Company; expectations regarding potential milestones; and the Company's strategy, business plans and focus.