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UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

 

FORM 8-K

 

 

CURRENT REPORT

Pursuant to Section 13 or 15(d) 

of the Securities Exchange Act of 1934

 

Date of Report (Date of Earliest Event Reported): November 5, 2019

 

 

Blueprint Medicines Corporation

(Exact name of registrant as specified in its charter)

 

 

Delaware   001-37359 26-3632015

(State or other jurisdiction

of incorporation)

   (Commission File Number)

(I.R.S. Employer

Identification No.)

 

 45 Sidney Street

Cambridge, Massachusetts

   02139
(Address of principal executive offices)   (Zip Code)

 

 Registrant’s telephone number, including area code: (617) 374-7580

 

 

(Former name or former address, if changed since last report)

 

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

 

¨Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
¨Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
¨Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
¨Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

 

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

 

Emerging growth company ¨

 

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ¨

 

Securities registered pursuant to Section 12(b) of the Exchange Act:

 

Title of each class Trading symbol(s) Name of each exchange on which registered
Common stock, par value $0.001 per share BPMC Nasdaq Global Select Market

 

 

 

 

 

Item 2.02 Results of Operations and Financial Condition.

 

On November 5, 2019, Blueprint Medicines Corporation (the “Company”) announced its financial results for the quarter ended September 30, 2019 and other business highlights. The full text of the press release issued in connection with the announcement is furnished as Exhibit 99.1 to this Current Report on Form 8-K (the “Form 8-K”) and is incorporated by reference herein.

 

The information responsive to Item 2.02 of this 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 (the “Securities Act”), or the Exchange Act, except as expressly set forth by specific reference in such filing.

 

Item 7.01 Regulation FD Disclosure.

 

On November 5, 2019, the Company intends to make a slide presentation at its Research and Development Day. The slide presentation is furnished as Exhibit 99.2 to this Form 8-K and is incorporated by reference herein.

 

The information responsive to Item 7.01 of the Form 8-K, including Exhibit 99.2 attached hereto, is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of 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 or the Exchange Act, except as expressly set forth by specific reference in such filing.

 

Item 9.01 Financial Statements and Exhibits.

 

(d) Exhibits.

 

The following exhibits relating to Item 2.02 and Item 7.01 of this Form 8-K shall be deemed to be furnished and not filed:

 

Exhibit No.   Description
99.1   Press release issued by Blueprint Medicines Corporation on November 5, 2019
99.2   Presentation dated November 5, 2019
104   Cover Page Interactive Data File (embedded within the Inline XBRL document)

 

2

 

 

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: November 5, 2019 By: /s/ Jeffrey W. Albers
    Jeffrey W. Albers
    Chief Executive Officer

  

3

 

 

Exhibit 99.1

 

 

 

Blueprint Medicines Outlines Precision Therapy Research Vision, Provides Update on Discovery and Clinical-Stage Portfolio at R&D Day and Reports Third Quarter 2019 Financial Results

 

-- R&D Day presentation discloses four research programs demonstrating the transformative science, urgency and efficiency underpinning the company’s integrated precision medicine platform --

 

-- Enrollment target reached in Phase 3 VOYAGER trial of avapritinib in third-line GIST --

 

-- Initial data from PIONEER trial of avapritinib in indolent systemic mastocytosis
to be presented at ASH --

 

-- Planned new drug applications for avapritinib for advanced systemic mastocytosis and pralsetinib for previously treated RET fusion non-small cell lung cancer on track for submission to FDA in Q1 2020 --

 

CAMBRIDGE, Mass., November 5, 2019 – Blueprint Medicines Corporation (NASDAQ:BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, is hosting its first R&D Day in New York City today.

 

During the event, Blueprint Medicines will outline its vision to become a leading platform-enabled, fully-integrated, global precision therapy company. The R&D Day presentation will highlight opportunities to expand the reach of the company’s therapeutic candidates to broader patient populations, integrate and scale scientific, clinical and commercial capabilities to build therapeutic area leadership, and fully utilize the company’s scientific platform to design innovative medicines targeting novel kinase biology. In addition, today the company reported financial results and provided a business update for the quarter ended September 30, 2019.

 

“As we prepare to launch our first medicine and submit multiple additional marketing applications next year, today we are unveiling our next wave of internally discovered research and clinical-stage precision therapies with the potential to deliver durable clinical benefits to additional patient populations,” said Jeff Albers, Chief Executive Officer of Blueprint Medicines. “By fully leveraging our integrated research capabilities and reinvesting insights from our ongoing clinical programs, we continue to build a powerful research engine with the potential to deliver transformative treatment advances to patients as well as rapid and sustainable growth to Blueprint Medicines.”

 

R&D Day Presentation Areas of Focus

 

·Highlight the significant medical need in indolent systemic mastocytosis (SM), a rare disease characterized by debilitating and unpredictable symptoms despite best available therapy. Based on an improved understanding of the disease, Blueprint Medicines now estimates there are approximately 75,000 patients with SM in the major markets, which consist of the United States, France, Germany, Italy, Spain, United Kingdom and Japan.
·Announce a comprehensive strategy to address a broad population of patients with SM and other mast cell disorders with the company’s drug candidates avapritinib and BLU-263, a next-generation KIT inhibitor. Blueprint Medicines plans to submit an investigational new drug (IND) application to the U.S. Food and Drug Administration (FDA) for BLU-263 for indolent SM in the first half of 2020.

 

 

 

 

·Introduce two research programs targeting well-characterized resistance mutations in patients with EGFR-driven non-small cell lung cancer (NSCLC), highlighting Blueprint Medicines’ differentiated capability for designing highly selective investigational medicines that address tumor evolution and resistance to targeted therapy.
·Highlight a research program under Blueprint Medicines’ cancer immunotherapy collaboration with Roche targeting MAP4K1, which is believed to play a role in T cell regulation.

 

Third Quarter 2019 Highlights and Recent Progress

 

Avapritinib: Gastrointestinal stromal tumors (GIST)

 

·Completed target enrollment in the Phase 3 VOYAGER trial of avapritinib versus regorafenib in patients with third- and fourth-line GIST.
·Announced the FDA intends to administratively split the new drug application (NDA) for avapritinib into two separate NDAs (one for PDGFRA Exon 18 mutant GIST, regardless of prior therapy, and one for fourth-line GIST) and requested top-line data from the ongoing Phase 3 VOYAGER trial to inform its review of the proposed fourth-line GIST indication. The PDUFA action date for both indications is currently February 14, 2020. For the fourth-line indication, an extension of up to three months for the PDUFA action date will likely be required to enable Blueprint Medicines to provide the top-line VOYAGER data to the FDA.

 

Avapritinib: Systemic mastocytosis (SM)

 

·Completed enrollment of Part 1 of the Phase 2 PIONEER trial of avapritinib in patients with indolent SM.

 

BLU-782: Fibrodysplasia ossificans progressiva (FOP)

 

·Entered into an exclusive, worldwide license agreement with Clementia Pharmaceuticals, a subsidiary of Ipsen, for the development and commercialization of BLU-782 as a potential treatment for patients with FOP and other indications.

 

Key Upcoming Milestones

 

The company expects to achieve the following milestones in the fourth quarter of 2019:

 

·Present initial data from Part 1 of the Phase 2 PIONEER trial of avapritinib in indolent SM at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition.
·Initiate a Phase 3 trial evaluating pralsetinib in first-line RET-fusion NSCLC.
·Initiate a Phase 1b/2 trial in China evaluating fisogatinib in combination with CS1001, CStone Pharmaceuticals' anti-PD-L1 inhibitor, in patients with HCC.

 

The company expects to achieve the following milestones related to planned marketing applications in 2020:

 

·Submit an NDA to the FDA for avapritinib for the treatment of advanced SM based on data from the Phase 1 EXPLORER trial and Phase 2 PATHFINDER trial in the first quarter of 2020.
·Submit an NDA to the FDA for pralsetinib for the treatment of patients with RET-fusion NSCLC previously treated with platinum-based chemotherapy in the first quarter of 2020.

 

 

 

 

·Submit an NDA to the FDA for pralsetinib for the treatment of patients with MTC previously treated with an approved multi-kinase inhibitor in the first half of 2020.
·Submit a supplemental NDA to the FDA for avapritinib for the treatment of third-line GIST in the second half of 2020.

 

Third Quarter 2019 Financial Results

 

·Cash Position: As of September 30, 2019, cash, cash equivalents and investments were $594.5 million, as compared to $494.0 million as of December 31, 2018. This increase reflects net proceeds of approximately $327.4 million from the company's follow-on underwritten public offering of common stock, which closed in April 2019, partially offset by cash used in operations. Cash, cash equivalents and investments as of September 30, 2019 do not include the $25.0 million upfront payment received in connection with entering into the worldwide license agreement with Clementia Pharmaceuticals or an $8.0 million research milestone achieved under the Roche collaboration, both of which were earned in October 2019.
·Collaboration Revenues: Collaboration revenues were $9.1 million for the third quarter of 2019, as compared to $1.1 million for the third quarter of 2018. This increase was primarily due to revenue recognized under the CStone and Roche collaborations. During the third quarter of 2019, the company recognized $6.0 million in milestone revenue under the CStone collaboration compared to no revenue recognized for the same period in 2018. During the third quarter of 2019, the company recognized $3.1 million in revenue under the Roche collaboration compared to $1.1 million for the same period in 2018.
·R&D Expenses: Research and development expenses were $81.5 million for the third quarter of 2019, as compared to $64.6 million for the third quarter of 2018. This increase was primarily due to increased clinical and manufacturing expenses driven by the company’s lead programs and increased personnel expenses. Research and development expenses included $7.7 million in stock-based compensation expenses for the third quarter of 2019.
·G&A Expenses: General and administrative expenses were $25.6 million for the third quarter of 2019, as compared to $12.0 million for the third quarter of 2018. This increase was primarily due to increased personnel expenses and increased professional fees for commercial-readiness and other activities. General and administrative expenses included $7.3 million in stock-based compensation expenses for the third quarter of 2019.
·Net Loss: Net loss was $94.3 million for the third quarter of 2019, or a net loss per share of $1.93, as compared to a net loss of $72.7 million for the third quarter of 2018, or a net loss per share of $1.66.

 

Financial Guidance

 

Based on its current plans, Blueprint Medicines expects that its existing cash, cash equivalents and investments, together with the $25.0 million upfront cash payment received under its license agreement with Clementia and an $8.0 million research milestone achieved in the fourth quarter of 2019 under the Roche collaboration, but excluding any additional potential option fees, milestone payments or other payments from Roche, CStone Pharmaceuticals or Clementia Pharmaceuticals, will be sufficient to enable it to fund its operating expenses and capital expenditure requirements into the second half of 2021.

 

 

 

 

Conference Call Information

 

Blueprint Medicines will host a live webcast of its R&D Day event at 8:30 a.m. ET today. The webcast may be accessed under “Events and Presentations” 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 90 days following the call.

 

About Blueprint Medicines

 

Blueprint Medicines is a precision therapy company striving to improve human health. With a focus on genomically defined cancers, rare diseases and cancer immunotherapy, we are developing transformational medicines rooted in our leading expertise in protein kinases, which are proven drivers of disease. Our uniquely targeted, scalable approach empowers the rapid design and development of new treatments and increases the likelihood of clinical success. We are currently advancing three investigational medicines in clinical development, along with multiple research programs. For more information, visit www.BlueprintMedicines.com and follow us on Twitter (@BlueprintMeds) and LinkedIn.

 

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 plans and timelines for the development of avapritinib, pralsetinib, fisogatinib, and BLU-263, including the timing, designs, implementation, enrollment, plans and announcement of results regarding Blueprint Medicines’ ongoing and planned clinical trials for its drug candidates, including avapritinib, pralsetinib, fisogatinib and BLU-263; plans and timelines for nominating additional development candidates; plans and timelines for submitting an IND application to the FDA for BLU-263; plans and timelines for submitting marketing applications for avapritinib and pralsetinib; the potential benefits of Blueprint Medicines' current and future drug candidates in treating patients; plans, timelines and expectations for the FDA's review and administrative split of the NDA for avapritinib for the treatment of adult patients with PDGFRA Exon 18 mutant GIST, regardless of prior therapy, and fourth-line GIST; plans, timelines and expectations for top-line data from the VOYAGER trial; plans, timelines and expectations for the commercialization of avapritinib for the treatment of GIST, if approved by the FDA; potential benefits of the license agreement between Blueprint Medicines and Ipsen; expectations regarding Blueprint Medicines' existing cash, cash equivalents and investments; and Blueprint Medicines' strategy, goals and anticipated milestones, business plans and focus. The words "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 delay of any current or planned clinical trials or the development of Blueprint Medicines' drug candidates, including avapritinib, pralsetinib, fisogatinib and BLU-263, or licensed products, including BLU-782; the FDA's intent to administratively split the proposed indications for avapritinib into two separate NDAs, which may not mean that either indication is approved; a delay in the review of the proposed indications as a result of the administrative split of the current NDA; FDA concerns regarding whether the response rate in the fourth-line GIST population was reasonably likely to predict clinical benefit in that population; there can be no assurance that the FDA will not ask for additional clinical trials for avapritinib; there can be no assurance that the VOYAGER top-line data will be sufficient for the FDA's review of the proposed fourth-line indication or that there will not be a delay in the availability of VOYAGER top-line data; 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; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials; Blueprint Medicines' ability to develop and commercialize companion diagnostic tests for its current and future drug candidates; and the success of Blueprint Medicines' current and future collaborations and licensing arrangement, including its cancer immunotherapy collaboration with F. Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc., its collaboration with CStone Pharmaceuticals, and its license to Clementia Pharmaceuticals. 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 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.

 

 

 

 

Blueprint Medicines Corporation

Selected Condensed Consolidated Balance Sheet Data

(in thousands)

(unaudited)

 

   September 30,   December 31, 
   2019   2018 
Cash, cash equivalents and investments  $594,459   $494,012 
Working capital (1)   419,584    439,464 
Total assets   737,925    540,124 
Deferred revenue   41,331    46,167 
Total liabilities   221,581    121,115 
Total stockholders’ equity   516,344    419,009 

 

(1)    Blueprint Medicines defines working capital as current assets less current liabilities.

 

Blueprint Medicines Corporation

Condensed Consolidated Statements of Operations Data

(in thousands, except per share data)

(unaudited)

 

   Three Months Ended 
   September 30, 
   2019   2018 
Collaboration revenue  $9,139   $1,095 
Operating expenses:          
Research and development   81,453    64,562 
General and administrative   25,647    12,041 
Total operating expenses   107,100    76,603 
Other income (expense):          
Other income (expense), net   3,692    2,799 
Interest expense   (6)   (14)
Total other income   3,686    2,785 
Net loss  $(94,275)  $(72,723)
Net loss per share — basic and diluted  $(1.93)  $(1.66)
Weighted-average number of common shares used in net loss per share — basic and diluted   48,921    43,915 

 

 

 

 

Investor Relations Contact

 

Kristin Hodous

Sr. Manager, Investor Relations

617-714-6674

ir@blueprintmedicines.com

 

Media Relations Contact

 

Jim Baker

Vice President, Corporate Affairs

617-844-8236

media@blueprintmedicines.com

 

 

 

 

Exhibit 99.2

 

M © 2019 Blueprint Medicines Corporation

 

 
 

 

w e l c o m e JEFF ALBERS Chief Executive Officer

 

 
 

 

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I5 (++0;065, 7961,*;065:, (::<47;065: (5+ ,:;04(;,: 6-;/, C647(5@D: -<;<9, 7,9-694(5*, (5+ ;/, -<;<9, 7,9-694(5*, 6-;/, 4(92,;: 05 >/0*/ ;/, C647(5@ 67,9(;,: (9, 5,*,::(903@ :<)1,*; ;6 ( /0./ +,.9,, 6-<5*,9;(05;@ (5+ 90:2. 3

 

 
 

 

Our core mission and foundational principles Blueprint Medicines aims to deliver on the promise of precision medicine to improve and extend the lives of patients with cancer and rare diseases. HIGHLY SELECTIVE INHIBITORS PATIENT SELECTION ADAPTIVE ABILITY 4

 

 
 

 

Our core mission and foundational principles Blueprint Medicines aims to deliver on the promise of precision medicine to improve and extend the lives of patients with cancer and rare diseases. TRANSFORMATIVE BENEFIT Life-changing outcomes for patients URGENCY EFFICIENCY Expedited development and regulatory pathways Increased probability of success 5

 

 
 

 

P1)-#)/+%2 )-!#3).-: %7/%$)3%$ $%5%+./,%-3 .& !5!/1)3)-)" !-$ /1!+2%3)-)" PDGFRA D842V+ GIST1 &4 %ea!" &1., IND 3. )-)3)!+ NDA 24",)22).-B!eak#h!o$gh AVAPRITINIB #he!a % de"igna#ion2 RET+ NSCLC3 40 &3 %ea!" &1., IND 3. /+!--%$ )-)3)!+ NDA 24",)22).-20 0 B!eak#h!o$gh -20 PRALSETINIB #he!a % -40 -60 de"igna#ion4 -80 -100 1. D!3! /1%2%-3%$ !3 ASCO 2019 A--4!+ M%%3)-' .-J4-% 1, 2019. D!3! #43.&& $!3%: N.5%,"%1 16, 2018. 2. A5!/1)3)-)" '1!-3%$ B1%!*3(1.4'( T(%1!/8 D%2)'-!3).-&.1 3(% 31%!3,%-3 .& /!3)%-32 6)3( 4-1%2%#3!"+% .1 ,%3!23!3)# GIST (!1".1)-' 3(% PDGFRA D842 ,43!3).-. 3. D!3! /1%2%-3%$ !3 ASCO A--4!+ M%%3)-' )-J4-% 2019. I-#+4$%2 NSCLC /!3)%-32 31%!3%$ !3 3(% 1%#.,,%-$%$ P(!2% 2 $.2% .& 400 ,' QD !-$ %-1.++%$ !2 .& N.5%,"%1 14, 2018 6)3( &.++.6-4/ 3(1.4'( ! $!3! #43.&& $!3% .& A/1)+ 28, 2019. 4. P1!+2%3)-)" '1!-3%$ B1%!*3(1.4'( T(%1!/8 D%2)'-!3).-&.1 3(% 31%!3,%-3 .& /!3)%-32 6)3( RET-&42).-/.2)3)5% NSCLC 3(!3 (!2 /1.'1%22%$ &.++.6)-' /+!3)-4,-"!2%$ #(%,.3(%1!/8 !-$ &.1 3(% 31%!3,%-3 .& /!3)%-32 6)3( RET ,43!3).--/.2)3)5% MTC 3(!3 1%04)1%2 2823%,)# 31%!3,%-3 !-$ &.1 6()#( 3(%1% !1% -. !##%/3!"+% !+3%1-!3)5% 31%!3,%-32. 6

 

 
 

 

The &a%id e*$!)(i$# $f B!)e%&i#( Medici#e' IMAGINING A NEW PL ATFORM BUILD ING THE PIPELINE R EALIZING THE VISI ON 2011 2014 2015 2019 2020 F UTURE RAPI D C LI NI CAL PRO O F -O F-CO NCEPT ACRO SS MU LT IPLE PR OGR A M S HIGH LY SELECTIVE KI NASE MEDI CI NE DISCOVERY PL ATFORM I#(eg&a(ed c$""e&cia!i.a(i$# I#dica(i$# e,%a#'i$# The&a%e)(ic a&ea !eade&'hi% I##$*a(i*e i#a'e bi$!$g-a*a%&i(i#ib A*a%&i(i#ib i# ad*a#ced '-'(e"ic "a'($c-($'i': cha#ge i# 'e&)" (&-%(a'e1 Ki#$"e i!!)'(&a(i$# &e%&$d)ced c$)&(e'-$f Ce!! Sig#a!i#g Tech#$!$g-, I#c. (+++.ce!!'ig#a!.c$") (CSTI). The f$&eg$i#g +eb'i(e i' "ai#(ai#ed b-CSTI, a#d B!)e%&i#( Medici#e' i' #$( &e'%$#'ib!e f$& i(' c$#(e#(. 1 Da(a %&e'e#(ed a( (he E)&$%ea# He"a($!$g-A''$cia(i$# A##)a! Mee(i#g i# J)#e 2019. Da(a c)($ff da(e: Ja#)a&-2, 2019. 7

 

 
 

 

O*' f%c*( )%da.: )h'ee !e. )he#e( RAPI D C LI NI CAL PRO O F -O F-CO NCEPT ACRO SS MU LT IPLE PR OGR A M S HIGH LY SELECTIVE KI NASE MEDI CI NE DISCOVERY PL ATFORM I$)eg'a)ed c%##e'c a" /a) %$ I$d ca) %$ e-&a$( %$ The'a&e*) c a'ea "eade'(h & I$$%+a) +e ! $a(e b %"%g. a+a&' ) $ b A+a&' ) $ b $ ad+a$ced (.()e# c #a()%c.)%( (: cha$ge $ (e'*# )'.&)a(e1 K $%#e ""*()'a) %$ 'e&'%d*ced c%*')e(. %f Ce"" S g$a" $g Tech$%"%g., I$c. (,,,.ce""( g$a".c%#) (CSTI). The f%'eg% $g ,eb( )e ( #a $)a $ed b. CSTI, a$d B"*e&' $) Med c $e( ( $%) 'e(&%$( b"e f%' )( c%$)e$). 1 Da)a &'e(e$)ed a) )he E*'%&ea$ He#a)%"%g. A((%c a) %$ A$$*a" Mee) $g $ J*$e 2019. Da)a c*)%ff da)e: Ja$*a'. 2, 2019. 8 IMAGINING A NEW PL ATFORM BUILD ING THE PIPELINE R EALIZING THE VISI ON 20 11 2014 2015 2019 2020 F UTURE

 

 
 

 

We aim "o make " an!fo ma"i$e p eci!ion "he apie! and e&pand "hei applica"ion "o addi"ional pa"ien" pop#la"ion! o$e "ime INDIC ATION EX PANSION Add e!! di!ea!e Add e!! di!ea!e e$ol#"ion 4 he"e ogenei"' E&pand "o ne% pop#la"ion! 3 Pa"ien" !elec"ion Combina"ion and !eq#en"ial " ea"men" 2 Fa!" e&pan!ion !" a"eg' Change "he pa adigm app oache! on ea POC l' Ta ge" !ingle d i$e 5 T#mo agno!"ic " ea"men" and p e$en"a"i$e combina"ion! Selec"i$e and po"en" inhibi"o 1 Patient population Discrete Expanded 9

 

 
 

 

We aim to make transformative precision therapies and expand their application to additional patient populations over time INDIC ATION EX PANSION A next-generation KIT inhibitor for mast cell disorders 10

 

 
 

 

With a cornerstone precision therapy we can rapidly reinvest insights and realize efficiencies THERAPEUTIC AREA LEADERSHIP Next-generation inhibitors Combination strategies Enhanced patient selection CLINICAL AND COMMERCIAL SCALE TRANSL ATIONAL INSIGHTS 11

 

 
 

 

With a cornerstone precision therapy we can rapidly reinvest insights and realize efficiencies THERAPEUTIC AREA LEADERSHIP for treatment-resistant non-small cell lung cancer 12

 

 
 

 

O!r scien ific pla form enables !s o e$plore ne# kinase biolog%, INNO VATION represen ing e"en larger oppor !ni ies o impac pa ien care GENETIC DRIVERS IMMUNOKINASES NOVEL BIOLOGY H!man kinome Kinome ill!s ra ion reprod!ced co!r es% of Cell Signaling Technolog%, Inc. (###.cellsignal.com) (CSTI). The foregoing #ebsi e is main ained b% CSTI, and Bl!eprin Medicines is no responsible for i s con en . 13

 

 
 

 

Our scientific platform enables us to e!plore ne kinase biolog", iNNO VATiON representing even larger opportunities to impact patient care immunokinase inhibitor 14 MAP4K1 is a collaboration target under the cancer immunotherap" collaboration ith Roche

 

 
 

 

EA$L)-% &A GE LA&E-% &A GE $EG'LA&" $) DI%C"(E$) A##$"(ED DE(EL"# E !& DE(EL"# E !& %'B I%%I"! A=*892;262+ (KI& & #DGF$A) #DGF$A GI%&1,2 4L GI%&1,2 3L GI%&1,2 2L GI%&1,2 A-=*6,.-% 2 I6-74.6; % 2 #9*4:.;262+, /795.94@ BL'-667 ($E&) 2L $E&+ !%CLC1,2 1L $E&+ !%CLC1,2 EGF$+ !%CLC (+7:25.9;262+)1,2 2L &C1,2 ";1.9 $E&-*4;.9.-:742-;<579:1,2 F2:70*;262+, /795.94@ BL'-554 (FGF$4) A-=*6,.-HCC2 A-=*6,.-HCC (+C%-1001)2 BL'-263 (KI&) I6-74.6; % BL'-782 (ALK2) F"#3 (EGF$+ C797% -7<+4. 5<;*6;) EGF$+ !%CLC1 (EGF$+ &790IC797% ;9284. 5<;*6;) EGF$+ !%CLC1 (2 <6-2:,47:.-;*90.;:) ( A#4K1)4 (3 <6-2:,47:.-255<67326*:. ;*90.;:)4 7607260 79 ,7584.;.-84*66.-1. '69.:.,;*+4. 79 5.;*:;*;2, -2:.*:.. 2. C%;76. #1*95*,.<;2,*4: 1*: .?,4<:2=. 9201;: ;7 -.=.478 *6-,755.9,2*42A. *=*892;262+, 89*4:.;262+ *6-/2:70*;262+ 26 *264*6-C126*, H760 K760, *,*< *6-&*2>*6. B4<.8926; .-2,26.: 9.;*26: *44 9201;: 26 ;1. 9.:; 7/ ;1. >794-. 3. C4.5.6;2* #1*95*,.<;2,*4: 1*: .?,4<:2=., >794->2-. 9201;: ;7 -.=.478 *6-,755.9,2*42A. BL'-782. 4. I6 ,744*+79*;276 >2;1 $7,1.. B4<.8926; .-2,26.: 1*: '.%. ,755.9,2*4 9201;: /79 <8 ;7 ;>7 89709*5:. $7,1. 1*: >794->2-. ,755.9,2*42A*;276 9201;: /79 <8 ;7 ;>7 89709*5: *6-.?-'.%. ,755.9,2*42A*;276 9201;: /79 <8 ;7 ;>7 89709*5:. 15 1L, /29:;-426.; 2L, :.,76--426.; 3L, ;129--426.; 4L, /7<9;1-426.; F"#, /2+97-@:84*:2* 7::2/2,*6: 89709.::2=*; GI%&, 0*:;9726;.:;26*4 :;975*4 ;<579:; HCC, 1.8*;7,.44<4*9 ,*9,2675*; &C, 5.-<44*9@ ;1@972-,*6,.9; !%CLC, 676-:5*44 ,.44 4<60 ,*6,.9. !DA !DA !DA I AA !DA I AA !DA !DA

 

 
 

 

S%bmi$$ed and !lanned Ne' D"%g A!!lica$i n# in 2020 Q1 2020* Q2 2020 Q3 2020 Q4 2020 GIST PDGFRA EXON 18 GIST PDUFA date: Feb 14, 2020 3L GIST 4L GIST PDUFA date: Feb 14, 2020 #%bmi$$ed !lanned * A##%me# admini#$"a$i&e #!li$ b) FDA in$ $' #e!a"a$e NDA# f " !" ! #ed indica$i n# %nde" ini$ial NDA #%bmi$$ed f " a&a!"i$inib in GIST and 16 e($en#i n f %! $ 3 m n$h# f " $he PDUFA da$e f " $he 4L indica$i n. PDUFA. P"e#c"i!$i n D"%g U#e" Fee Ac$

 

 
 

 

S%bmi$$ed and !lanned Ne' D"%g A!!lica$i n# in 2020 Q1 2020* Q2 2020 Q3 2020 Q4 2020 GIST PDGFRA EXON 18 GIST PDUFA da e: Feb 14, 2020 3L GIST 4L GIST PDUFA da e: Feb 14, 2020 SM ADVANCED SM #%bmi$$ed !lanned * A##%me# admini#$"a$i&e #!li$ b) FDA in$ $' #e!a"a$e NDA# f " !" ! #ed indica$i n# %nde" ini$ial NDA #%bmi$$ed f " a&a!"i$inib in GIST and 17 e($en#i n f %! $ 3 m n$h# f " $he PDUFA da$e f " $he 4L indica$i n. PDUFA, P"e#c"i!$i n D"%g U#e" Fee Ac$

 

 
 

 

S%bmi$$ed and !lanned Ne' D"%g A!!lica$i n# in 2020 Q1 2020* Q2 2020 Q3 2020 Q4 2020 GIST PDGFRA EXON 18 GIST PDUFA da e: Feb 14, 2020 3L GIST 4L GIST PDUFA da e: Feb 14, 2020 SM ADVANCED SM RET 2L NSCLC 2L MTC #%bmi$$ed !lanned * A##%me# admini#$"a$i&e #!li$ b) FDA in$ $' #e!a"a$e NDA# f " !" ! #ed indica$i n# %nde" ini$ial NDA #%bmi$$ed f " a&a!"i$inib in GIST and 18 e($en#i n f %! $ 3 m n$h# f " $he PDUFA da$e f " $he 4L indica$i n. PDUFA, P"e#c"i!$i n D"%g U#e" Fee Ac$

 

 
 

 

R&D Da+ age!da Jeff Albers, Chief E*ec'&i(e Office$ We c" e a!d c" #a!+ (i%i"! Cern Akin, MD, PhD, P$"fe%%"$ "f Medici!e, U!i(e$%i&+ "f Michiga! And Boral, MD, PhD, Chief Medica Office$ S" (i!g #a&ie!& !eed% i! %+%&eic a%&"c+&"%i% Christina Rossi, Chief C" e$cia Office$ Q&A , Pa$& 1 Marion Dorsch, PhD, Chief Scie!&ific Office$ A #$" ific # a&f"$ f"$ #$eci%i"! edici!e Tirn Gu!i, PhD, Se!i"$ Vice P$e%ide!&, Che i%&$+ Add$e%%i!g &' "$ e(" '&i"! i! '!g ca!ce$ Klaus Hoeflich, PhD, Vice P$e%ide!&, Bi" "g+ Ca!ce$ i '!"&he$a#+: a !e) f$"!&ie$ Q&A , Pa$& 2 Jeff Albers, Chief E*ec'&i(e Office$ C "%i!g $e a$k% 19 BREAK

 

 
 

 

[LOGO]

 

 
 

 

Addressing patient needs in systemic mastocytosis Cern Akin, M.D., Ph.D. Professor of Medicine, University of Michigan Andy Boral, M.D., Ph.D. Chief Medical Officer Christy Rossi Chief Commercial Officer J D v ng w th SM

 

 
 

 

Systemic mastocytosis is one disease with a common genetic driver KIT D816V mutation frequency AD VANCED SYSTEMIC MASTO CYTO SIS -95% of patients INDOLENT SYSTEMIC MASTO CYTO SIS 22

 

 
 

 

Overview of indolent systemic mastocytosis CEM AKIN, MD, PhD Professor of Medicine, University of Michigan

 

 
 

 

Di$cl!$&#e$ ) ) Cem Aki MD PhD I i 'e$%iga%!#: Bl&e"#i % Medici e$* ! g!i g Pha$e 2 PIONEER %#ial i d!le % $($%emic ma$%!c(%!$i$ ) ) C! $&l%a %: Bl&e"#i % Medici e$ N!'a#%i$ A'a"#i%i Medici ib i$ a i 'e$%iga%i! al age % bei g de'el!"ed b( Bl&e"#i % e$ a d ha$ !% bee a""#!'ed b( %he F!!d ad D#&g Admi !# a i$%#a%i! !# a ( !%he# heal%h a&%h!#i%( f!# &$e i %he U i%ed S%a%e$ ( !%he# j&#i$dic%i! f!# a ( i dica%i! 24

 

 
 

 

Pa/%!)/ 1 7 I) *'!)/ SM 6 6 6 6 6 6 6 6 45-4!a--*' "!(a'! Ha *).!/ *" .&%) '!.%*). a/ a#! 7 D%a#)*.! a/ a#! 14 b4 a .&%) b%*+.4 I)%/%a''4 *)'4 .4(+/*(. 2!-! .&%) '!.%*). a) !3!-c%.! %) 0c! 2$!!5%)# 29 4!a-. Na0.!a, %a--$!a, %)c-!a.! %/c$%)#, "'0.$%)#, b*)! +a%) Pa..! *0/ /2%c!, b'** +-!..0-! 2a. 0) !/!c/ab'! 30 4!a-. B*)! (a--*2 b%*+.4 20% %)"%'/-a/%*) 2%/$ (a./ c!''.. T-4+/a.! 76 )#/(' S4(+/*(. +-*#-!..! *1!-/$! )!3/ 10 4!a-., -!ac/%)# /* .c!)/., +!-"0(!., %)c-!a.%)# b*)! +a%), "'0.$%)#, '%#$/$!a ! )!.., "a/%#0! 6 6 6 U'/-a1%*'!/ /$!-a+4 0)ab'! /* c*)/-*' .&%) .4(+/*(. S/a-/! .a'%)! %)"0.%*). (*)! '%/!-) !1!-4 */$!-2!!&, $a a +*-/ +'ac! . P-*#-!..%1! '*.. *" ,0a'%/4 *" '%"! 25

 

 
 

 

Pa* e%* 1 1 I%d&#e%* SM 0 Med ca* &%): 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Ce* ( / %e 10 $g da #. Fe-&fe%ad %e 180 $g da #. M&%*e#+"a)* 10 $g da #. Be%ad(.# e,e(. 4-6 h&+() H.d(&-./ %e a) %eeded D c#&fe%ac a) %eeded E' Pe% a) %eeded O$a# /+$ab &%ce $&%*h#. O$e'(a/&#e da #. Z&f(a% da #. Ra% * d %e 300 $g da #. E%*ec&(* 6 $g da #. T&'a$a-Sa# %e %f+) &%) %!ec* &% 26

 

 
 

 

Pa,"e&, 2 4 I&d'$e&, SM 3 3 3 3 3 51-1ea*-'$d %a$e S#"& $e+"'&+ a+ a ,ee&a e* D"a &'+ed a, a e 31 b1 +#"& b"'(+1 T*1(,a+e /a+ 15, a&d &' b'&e %a**'/ b"'(+1 /a+ (e*f'*%ed "&","a$$1 A 4 e 47: De.e$'(ed $"fe-,!*ea,e&"& +1%(,'%+ E("+'de+ 'f abd'%"&a$ c*a%("& c'&+c"'-+&e++ , f$-+!"& , +!'*,&e++ 'f b*ea,!, c!e+, (a"& a&d dec*ea+e "& 4 A Ca*d"ac ca,!e,e*"2a,"'& 20% 'cc$-+"'& e 49: Da"$1 e("+'de+, b'&e %a**'/ b"'(+1: 3 %"&'* c*",e*"a f'* SM; (*e+c*"bed E("Pe&, 3 fe0'fe&ad"&e, $e.'ce,"*"2"&e, %'&,e$-#a+,, *a&","d"&e, c*'%'$1& 3 3 I&","a,ed (*ed&"+'&e 10 % da"$1 a&d "&","a,ed '%a$"2-%ab (*ea((*'.a$ b-, de&"ed 3 da1+ $a,e*, !ad a !1(',e&+".e e.e&, a&d !ad a %1'ca*d"a$ "&fa*c,"'&, ca*d"ac a**e+,, *e)-"*"& *e+-+c",a,"'&. T*1(,a+e /a+ 178 d-*"& e.e&,. 3 S,a*,ed '%a$"2-%ab a&d %"d'+,a-*"& /",! c'&,*'$ 'f $"fe ,!*ea,e&"& a,,ac#+ b-, c'&,"&-a,"'& 'f fa," -e, +#"& +1%(,'%+ a&d d"a**!ea 3 D"+c'&,"&-ed %"d'+,a-*"& d-e ,' &a-+ea a&d .'%","& 27

 

 
 

 

Urticaria pigmentosa in a patient with indolent SM 28 Patient permission granted for use of photos.

 

 
 

 

Healthy mast cells play a key role in the immune-inflammatory response Healthy mast cells ALLERGENS, TOXINS, HEAT Transient activation Release mediators 29 STIMULUS MAST CELL MORPHOLOGY MAST CELL ACTIVITY

 

 
 

 

In nea"l' all SM !a$ en$#, KIT D816V abe""an$l' ac$ &a$e# ma#$ cell# Heal$h' ma#$ cell# ALLERGENS, TOXINS, HEAT T"an# en$ ac$ &a$ n Relea#e med a$ "# S! ndle-#ha!ed ma#$ cell# Abe""an$ ac$ &a$ n P" l fe"a$ n & acc%m%la$ n KIT D816V O"gan nf l$"a$ n Relea#e med a$ "# 30 STIMULUS MAST CELL MORPHOLOGY MAST CELL ACTIVITY

 

 
 

 

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diag"#&'ic c%i'e%ia1 S,&'e!ic !a&'#c,'#&i& C i"ica fi"di"g i"dica'i)e #f #%ga" da!age +/-#'he% he!a'# #gic di&#%de% ALL SYSTEMIC MASTOCYTOSIS AD VANCED ON LY 32 1 Va e"', e' a . 8 ##d, 2016.

 

 
 

 

I-$.+%-3 SM /!3)%-32 1%/.13 ()'( 28,/3., "41$%-F1%04%-#8 .& ,.$%1!3% 3. 2%5%1% 28,/3.,2 6)3()-+!23 8%!1, $%2/)3% "%23 !5!)+!"+% 3(%1!/8 34 M!23 C%++ C.--%#3 1%')2318 $!3! .-&)+%. E-1.++,%-3 )-)3)!3%$ D%#%,"%1 1, 2015. D!3! #43.&& $!3%: A4'423 20, 2019. ISM (n=109) AdvSM (n=15) Gastrointestinal symptoms A"$.,)-!+ /!)-B+.!3)-' D)!11(%! N!42%! F+!34+%-#% .,)3)-' Skin symptoms I3#()-' F+42()-' S*)-#(!-'%2 50% 51% 39% 39% 29% 15% 52% 49% 49% 60% 60% 53% 73% 40% 60% 47% 40% 40% ISM (n=109) AdvSM (n=15) Systemic symptoms F!3)'4%/3)1%$-%22 * P!)-(-.3 !"$.,)-!+) H%!$!#(% S6%!3)-' S6%++)-' A-!/(8+!7)2 D)&&)#4+38 "1%!3()-' 75% 55% 45% 34% 32% 35% 29% 87% 60% 40% 47% 40% 40% 47%

 

 
 

 

I-$.+%-3 SM /!3)%-32 1%/.13 ()'( 28,/3., "41$%-F1%04%-#8 .& ,.$%1!3% 3. 2%5%1% 28,/3.,2 6)3()-+!23 8%!1, $%2/)3% "%23 !5!)+!"+% 3(%1!/8 34 M!23 C%++ C.--%#3 1%')2318 $!3! .-&)+%. E-1.++,%-3 )-)3)!3%$ D%#%,"%1 1, 2015. D!3! #43.&& $!3%: A4'423 20, 2019. ISM (n=109) AdvSM (n=15) Gastrointestinal symptoms A"$.,)-!+ /!)-B+.!3)-' D)!11(%! N!42%! F+!34+%-#% .,)3)-' Skin symptoms I3#()-' F+42()-' S*)-#(!-'%2 50% 51% 39% 39% 29% 15% 52% 49% 49% 60% 60% 53% 73% 40% 60% 47% 40% 40% ISM (n=109) AdvSM (n=15) Systemic symptoms F!3)'4%/3)1%$-%22 * P!)-(-.3 !"$.,)-!+) H%!$!#(% S6%!3)-' S6%++)-' A-!/(8+!7)2 D)&&)#4+38 "1%!3()-' 75% 55% 45% 34% 32% 35% 29% 87% 60% 40% 47% 40% 40% 47%

 

 
 

 

6<(-363(.&0 .14&(7 3+ ).6*&6* 6<147316 .6 3+7*2 6*9*5* >60% of patients with systemic mastocytosis and other mast cell disorders (n=420) reported their ability to cope was moderately to extremely affected, despite best available therapy A2&4-<0&(7.( *4.63)*6 F*&5/&2;.*7< 2&'.0.7< 73 :35//4&57.(.4&7* F&7.,8* $245*).(7&'.0.7< G&6753.27*67.2&0 (3140&.276 &.2 0.0% 20.0% E;75*1* 40.0% M3)*5&7* 60.0% A 0.770* 80.0% 100.0% ". J*22.2,6, N. !866*00, B. J*22.2,6, %. "0**, L. "7*50.2,, M. C&67*006, et a/.#-* M&673(<736.6 "3(.*7< 6859*< 32 1&67 (*00 ).635)*56: 4&7.*27 *;4*5.*2(*6 &2) 4*5(*47.326; J A00*5,< C0.2 118230 5&(7, 2 (2014), 44. 70-76. 35 15.3% 12.9% 23.0% 11.6% 26.1% 35.6% 27.7% 21.4% 24.3% 30.3% 32.7% 22.2% 43.5% 27.4% 16.9% 30.9% 34.6% 20.1% 19.0% 33.5% 25.9%

 

 
 

 

Pa.%!).-1%.$ %) *'!). SM $a0! -%#)%"%ca). +*'2+$a,(ac2 b/, !) -75% *" ISM +a.%!).-$a0! .a&!) 34 c'a--!-*" ,/#-.* (a)a#! .$!%, %-!a-! # of drug classes 8+ 14% 5% 3 18% 7 13% 4 20% 20% 5 8% N=103 36 I) *'!). S2-.!(%c Ma-.*c2.*-%-S2(+.*( A--!--(!). F*,( (ISM-SAF) Ob-!,0a.%*)a' S./ 2 J/'2 2018 Da.a c/.*"": Ma,c$ 2018 1 2 3 4 5 7 8+

 

 
 

 

Target profile for a disease-modifying therapy for systemic mastocytosis Reduces mast cell burden and systemic symptoms Reduces polypharmacy burden Targets the K T D816V driver mutation 37

 

 
 

 

Avapritinib for indolent systemic mastocytosis ANDY BORAL, MD, PhD Chief Medical Officer

 

 
 

 

S1,-!'%c 'a,-)c1-),%, +!*+!,!(-, -$! &a+#!,-)**)+-.(%-1 ")+ a/a*+%-%(%b U.S. REGULATORY SUBMISSION PLANS LATE CLINICAL DEVELOPMENT KIT D816V ADVANCED SM Q1 2020 INDOLENT SM K%()'! %&&.,-+a-%)( +!*+) .c! c).+-!,1 )" C!&& S%#(a&%(# T!c$()&)#1, I(c. (000.c!&&,%#(a&.c)') (CSTI). T$! ")+!#)%(# 0!b,%-! %, 'a%(-a%(! b1 CSTI, a( B&.!*+%(-M! %c%(!, %, ()-+!,*)(,%b&! ")+ %-, c)(-!(-. 39

 

 
 

 

A5"01*3*.*# 6"2 20&$*'*$",,7 %&2*(.&% 3/ *.)*#*3 KIT 0816 R7%"039 (-*%/23"41*.) G,&&5&$9 (*-"3*.*#) "5"01*3*.*# -"2*3*.*# 1*01&3*.*# B*.%*.( 3/ KIT B*.%*.( 3/ /3)&1 +*."2&2 (2*8& *2 01/0/13*/.", 3/ #*.%*.() B*/$)&-*$", #*.%*.( #7 0*2$/5&1R! "3 34M *E5".2 EK &3 ",. S$* T1".2, M&%. 2017;9(414). #B,4&01*.3 M&%*$*.&2 *.3&1.", %"3" /. '*,&. K*./-& *,,4231"3*/.2 1&01/%4$&% $/413&27 /' C&,, S*(.",*.( T&$)./,/(7, I.$. (CSTI) (666.$&,,2*(.",.$/-). B,4&01*.3 M&%*$*.&2 *2 ./3 1&20/.2*#,& '/1 3)& $/.3&.3 /' 3)& CSTI 2*3&. T)& 31"%&-"1+2 "00&"1*.( *. 3)*2 01&2&.3"3*/. "1& 3)& 01/0&137 /' 3)&*1 1&20&$3*5& /6.&12. 40 KIT D816V biochemicai iC50 "5"01*3*.*#* *-"3*.*#* -"2*3*.*## -*%/23"41*.* 1*01&3*.*## 0.27 .M 8150 .M >1000 .M 2.9 .M 2.6 .M

 

 
 

 

E"PLORER &#4# 3*07'& 120(05/& %-+/+%#-#%4+6+48 +/ 1#4+'/43 7+4* #&6#/%'& M BEST RESPONSE PER I!G-MRT-ECNM CRITERIA1 ALL DOSES (N=39) BREAKTHRO GH THERAP" DESIGNATION2 77% C0/(+2.'& ORR 74% 12-.0/4* DOR 2#4' P-#/ 40 35$.+4 NDA (02 #6#12+4+/+$ (02 #&6#/%'& M +/ Q1 2020, $#3'& 0/ %0.$+/'& &#4# (20. E"PLORER #/& PA!HFINDER 42+#-3 9 9 9 9 9 A6#12+4+/+$ 7#3 )'/'2#--8 7'---40-'2#4'& M034 #&6'23' '6'/43 2'1024'& $8 +/6'34+)#4023 7'2' G2#&' 1 02 2 66% 0( 1#4+'/43 *#& G2#&' 3 #/& 4 42'#4.'/4-2'-#4'& AE3 C8401'/+#3 7'2' 4*' .034 %0..0/ G2#&' 3 #/& 4 42'#4.'/4-2'-#4'& AE A%2033 #--&03'3, 4% 0( 1#4+'/43 &+3%0/4+/5'& 42'#4.'/4 &5' 40 42'#4.'/4-2'-#4'& AE3 SAFET" (#= 69) 1 D#4# 12'3'/4'& #4 4*' E5201'#/ H'.#40-0)8 A330%+#4+0/ A//5#-M''4+/) +/ J5/' 2019. D#4# %540(( &#4': J#/5#28 2, 2019. 2 A6#12+4+/+$ )2#/4'& B2'#,4*205)* !*'2#18 D'3+)/#4+0/ (02 4*' 42'#4.'/4 0( #&6#/%'& M, +/%-5&+/) 4*' 35$481'3 0( #))2'33+6'M, M 7+4* #/ #330%+#4'& *'.#40-0)+% /'01-#3. #/& .#34 %'---'5,'.+#. ORR, 06'2#--2'310/3' 2#4'; DOR, &52#4+0/ 0( 2'310/3'; AE, #&6'23' '6'/4. 41

 

 
 

 

Disease spectrum across s"stemic mastoc"tosis and other mast cell disorders Life-threatening impact Requirement for high treatment intensit" Requirement for long-term therap" 42 Debilitating s"mptoms Mast cell disorders Mast cell activation s"ndrome Hereditar" alpha tr"ptasemia Severe mast cell mediated asthma Severe anaph"la!is ndolent SM ndolent SM Smoldering SM Advanced SM Aggressive SM SM ith an associated hematologic neoplasm Mast cell leukemia

 

 
 

 

Comprehensive systemic mastocytosis clinical trial program Advanced SM Phase 1 dose-escalation trial with open-label expansion Advanced SM Phase 2 single-arm trial 43

 

 
 

 

I'd(%e', SM )a,#e',+ e'*(%%ed #' EXPLORER ,*#a% "ad dee) *ed-c,#('+ (' (b$ec,#.e &ea+-*e+ ( &a+, ce%% b-*de' Se*-& ,*0),a+e Ma**(/ &a+, ce%%+ S)%ee' .(%-&e Ma**(/ KIT D816V 44 Da,a )*e+e',ed a, ,"e E-*()ea' He&a,(%(!0 A++(c#a,#(' A''-a% Mee,#'! #' J-'e 2019. Da,a c-,( da,e Ja'-a*0 2, 2019.

 

 
 

 

EXPLORER " / .&+2 ISM *" SSM , /'#*/. 2'/& (+*% "0-/'+*. +$ /&#-,3 / (+2 "+.#. 4 4 14 +$ 15 (93%) -#) '* +* /-# /)#*/ 0, /+ *# -(3 3 3# -. (!3!(# 36) C0--#*/ 1#-%# "+.# '. 126 )% 2'/& 73% *+2 /-# /#" / 100 )% QD N#2 * (3.'. $-+) EXPLORER /-' (. D / !0/+$$ " /# J *0 -3 2, 2019. ISM, '*"+(#*/ SM; QD, +*!# " '(3; SSM, .)+("#-'*% SM. 45

 

 
 

 

E# LO!E! '$5$ 4+18(' 3('6&5,10 ,0 21.:2+$3/$&: %63'(0 Polypharmacy Burden in Indolent SM2 D36* &.$44 % 1) 2$5,(054 5+$5 +$7( 3(&(,7(' 5+,4 5:2( 1) 53($5/(05 Advanced SM +$4( 1 '14(-(4&$.$5,10 53,$. 8,5+ 12(0-.$%(. (92$04,10 H1 A05,+,45,/,0(4 H2 A05,+,45,/,0(4 C31/1.:0 "1',6/ L(6-153(,0( I0+,%,5134 Concomitant Medication Analysis1 O) 22 2$5,(054 8,5+ %$4(.,0( &135,&145(31,'4: ; ; 18/22 (80%) '(&3($4(' 5+(,3 45(31,' '14( 9/22 (41%) ',4&105,06(' 5+(,3 45(31,'4 (05,3(.: 0% 20% 40% 60% 80% 100% N=103 1 D$5$ 23(7,164.: 23(4(05(' $5 A"H A006$. M((5,0* ,0 D(&(/%(3 2018. D$5$ &651)) '$5(: "(25(/%(3 30, 2018. 2 I0'1.(05 ":45(/,& M$451&:514,4 ":/251/ A44(44/(05 F13/ (I"M-"AF) O%4(37$5,10$. "56': J6.: 2018. D$5$ &651)) '$5( M$3&+ 2018. 49 98% 93% 66% 62% C135,&145(31,'4 55% E2,0(2+3,0( 31510 6/2 I0+,%,5134 A05,-I*E C:513('6&5,7( A*(054 48% 46% 18% 15%

 

 
 

 

45-1!a+-)& 0)'a( 0%-$ !/)&/%(# ,1,-!'%c 'a,-)c1-),%, MARROW CD117 (50% MC) COLON CD25 (>100 MCS/HPF) 2015: I( )&!(-,1,-!'%c 'a,-)c1-),%, 2016: A##+!,,%/! ,1,-!'%c 'a,-)c1-),%, 3 3 3 3 3 3 3 230 *).( 0!%#$-&),, %( *+%)+ 6 ')(-$, S-)'ac$, .) !(.', c)&)( MC %("%&-+a-%)( 5c' *a&*ab&! ,*&!()'!#a&1 A(!'%c ($!')#&)b%( 9.9#/ L) Ma++)0 MC, 50%, -+1*-a,! 562(#/'L E(+)&&! )( EXPLORER ,-. 1 SM-AHN )( c!(-+a& *a-$)&)#1 +!/%!0 50 asy cou sasyc y u y sse py ap y osay aay y Tc ay uoa y y o c ya sey ao usy y 0

 

 
 

 

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45-1!a+-)& 0)'a( 0%-$ !/)&/%(# ,1,-!'%c 'a,-)c1-),%, MARROW CD117 (50% MC) COLON CD25 (>100 MCS/HPF) 2015: I( )&!(-,1,-!'%c 'a,-)c1-),%, 2016: A##+!,,%/! ,1,-!'%c 'a,-)c1-),%, 3 3 3 3 3 3 3 230 *).( 0!%#$-&),, %( *+%)+ 6 ')(-$, S-)'ac$, .) !(.', c)&)( MC %("%&-+a-%)( 5c' *a&*ab&! ,*&!()'!#a&1 A(!'%c ($!')#&)b%( 9.9#/ L) Ma++)0 MC, 50%, -+1*-a,! 562(#/'L E(+)&&! )( EXPLORER ,-. 1 SM-AHN )( c!(-+a& *a-$)&)#1 +!/%!0 50 asy cou sasyc y u y sse py ap y osay aay y Tc ay uoa y y o c ya sey ao usy y 0

 

 
 

 

BONE MARROW MAST CELLS & SERUM TRYPTASE KIT D816V MUTANT ALLELE FRACTION WEIGHT SPLEEN VOLUME 51 Case courtesy of Dr. Deepti Radia, Guys and St. Thomas Trust. Data cutoff date: January 2, 2019.

 

 
 

 

COLON CD25 MARROW CD117 MRI ABDOMEN Cycle 3 Cycle 7 Cycle 3 52 Case courtesy of Dr. Deepti Radia Guys and St. Thomas Trust. Data cutoff date: January 2 2019. BASELINE ON STUDY

 

 
 

 

BASELINE 6 MONTHS 29 MONTHS Case co rtes! of Dr. Deepti Radia, G !s and St. Thomas Tr st. Data c toff date: Jan ar! 2, 2019. atient permission ranted for se of photos 53

 

 
 

 

BASELINE 6 MONTHS 29 MONTHS Case co rtes! of Dr. Deepti Radia, G !s and St. Thomas Tr st. Data c toff date: Jan ar! 2, 2019. atient permission ranted for se of photos 54

 

 
 

 

Comprehensive s stemic mastoc tosis clinical trial program Advanced SM Phase 1 dose-escalation trial with open-label expansion Advanced SM Phase 2 single-arm trial Indolent SM Phase 2 randomi!ed, double-blind, placebo-controlled trial 55

 

 
 

 

PIONEER /-&a' !".&$)"! /* "1a'0a/" a1a+-&/&)&b &) &)!*'")/ SM PART 1 D*."-#&)!&)$ PART 2 R"$&./-a/&*)-")ab'&)$ 25 ($ QD a1a+-&/&)&b 50 ($ QD indolent SM P%a." 2 -"$&./-a/&*)-")ab'&)$ -a)!*(&5"!, +'a"b*-*)/-*''"! /-&a' &)+a/&")/. 2&/% &)!*'")/ SM RP2D R, 1:1 100 ($ QD O+")-'ab"' "3/").&*) +'a "b* P'a "b* 6 Eligibility: M*!"-a/"-/*-."1"-" &)!*'")/ *-.(*'!"-&)$ SM 6 Key endpoints: ISM-SAF /*/a' .4(+/*( . *-" (+-&(a-4), ,0a)/&/a/&1" ("a.0-". *# (a./ "'' b0-!"), .a#"/4 6 E)-*''(")/ *# Pa-/ 1 &. *(+'"/" 2&/% 39 +a/&")/. *) ./0!4; )* +a/&")/. %a1" !&.*)/&)0"! !0" /* a) a!1"-." "1")/ /* !a/"1 6 P'a) /* !&. '*." &)&/&a' !a/a #-*( Pa-/ 1 a/ ASH (""/&)$ &) D" "(b"-2019 6 I)1"./*-"1")/ a)! 2"ba./ +'a))"! #*-S0)!a4, D" "(b"-8 1 A. *# N*1"(b"-1, 2019. R, -a)!*(&5"!; RP2D, -" *((")!"! +a-/ 2 !*."; ASH (""/&)$, A("-& a) S* &"/4 *# H"(a/*'*$4 A))0a' M""/&)$ & E3+*.&/&*) 56

 

 
 

 

A comprehensive program for mast cell disorders CHRISTINA ROSSI Chief Commercial Officer

 

 
 

 

E:3$1'(' SM 23324671,6; %$5(' 21 ,1&4($5(' 71'(456$1',1* 2) 6+( ',5($5( SYSTEMIC MASTOCYTOSIS EPIDEMIOLOGY -75,000 34(8$/(16 3$6,(165 ,1 0$-24 0$4.(65 1 -20,000 patients $4( ,'(16,),$%/( 9,6+,1 &/$,05 '$6$ ,1 6+( 1,6(' S6$6(5 2 MOST AD LTS "ITH C TANEO S S#MPTOMS "ILL SHO" S#STEMIC DISEASE "HEN F LL# N!EST GATED M$-24 0$4.(65 ,1&/7'( S, E 5 $1' J$3$1. 1. C2+(1 S (6 $/ B4 J H$(0$62/ (2014) 166(4):521-8 $1' "24/' B$1. P237/$6,21 (56,0$6(5. 2. B/7(34,16 M(',&,1(5 $1$/;5,5 2) &/$,05 '$6$ )24 0$562&;625,5. 58

 

 
 

 

 

Foc$"ed effo!#" de"igned #o iden#if' a#ien#" and !ed$ce diagno"#ic dela' Tailo!ed heal#hca!e !o%ide! a&a!ene"" Pa#holog' and !efe!ence Ac#i%a#e a#ien# and lab a!#ne!"hi " ca!egi%e!" Educate on !ele%an# "ign" and "'m#om" b' " ecial#' In%e"# in data and insights #o efficien#l' #a!ge# Empower and educate o#en#ial $ndiagno"ed a#ien#" &i#h clea! call #o ac#ion Ini#ia#e "#!a#egic lab a!#ne!"hi #o enable solutions " Share best practices on ho& #o o #imall' "$" ec# & diagno"e AIM TO A CCELER ATE SYSTEMIC MASTOCYTOSIS DIAGNOSIS T IME LI N E S 59

 

 
 

 

We aim to make transformative precision therapies and expand their application to additional patient populations over time INDIC ATION EX PANSION A next-generation KIT inhibitor for mast cell disorders 60

 

 
 

 

Disease spectrum across s"stemic mastoc"tosis and other mast cell disorders Life-threatening impact Requirement for high treatment intensit" Requirement for long-term therap" 61 Debilitating s"mptoms Mast cell disorders Mast cell activation s"ndrome Hereditar" alpha tr"ptasemia Severe mast cell mediated asthma Severe anaph"la!is ndolent SM ndolent SM Smoldering SM Advanced SM Aggressive SM SM ith an associated hematologic neoplasm Mast cell leukemia

 

 
 

 

BLU-263 de"igned #o enable dee !each in#o #he ma"# cell di"o!de! " ec#!$m AVAPRITINIB BLU-263 62 Ma"# cell di"o!de!" Ma"# cell ac#i%a#ion "(nd!ome He!edi#a!( al ha #!(#a"emia Se%e!e ma"# cell media#ed a"#hma Se%e!e anah(la'i" Indolen# SM Indolen# SM Smolde!ing SM Ad%anced SM Agg!e""i%e SM SM &i#h an a""ocia#ed hema#ologic neola"m Ma"# cell le$kemia

 

 
 

 

BLU-263 2a. -a,'"(3 ,-+%-#..#" a.#" +* '*.'%&/. $-+) a1a,-'/'*' POTENT -*a*+)+(a-,+/#*!3 SELECTIVE H'%&(3 .#(#!/'1# $+-K T, 2'/& (+2 +$$-/a-%#/ a!/'1'/3 CNS PROFILE D#.'%*#" /+ *+/ !-+.. S0 a%a'*./ K T D816V (++"--a'* a--'#-PLAN TO SUBM T ND APPL CAT ON FOR NDOLENT SM TO FDA N 1H 2020 63 CNS, !#*/-a( *#-1+0. .3./#); ND a,,('!a/'+*, '*1#./'%a/'+*a( *#2 "-0% a,,('!a/'+*..

 

 
 

 

BLU-263: ",*-$))(+& -.$")(+(" ) -.,%()$ EQUIVALENT IN VIVO EFFICAC EQUIVALENT POTENC E%%(""4 (+ P815 (KIT D816Y) 01*,. *,#$) BLU-263 0.2 0.22 >10000 0.3 0.24 >10000 0.1 0.1 >10000 A2 I* -.(0(+(! 0(+(! DIFFERENTIATED SELECTIVIT AND CNS PROFILES N R 21.2 /,#(1* "' ++$) IC50 280 +M 0.40 >10 5M 0.024 0 K-,11 ',*,&$+ 0$ 64 BID, 03("$ # ()4. M$!+-*$ !.!)*%,%'%" BLU-263 KITPDGFRAKIT C(&)(-'# D816VD842VV560G/D816V IC50 (+M)IC50 (+M)IC50 (+M)

 

 
 

 

Ongoing a apritinib clinical trials AVAPRITINIB AVAPRITINIB AVAPRITINIB 65 Mast cell disorders Mast cell actiation s#ndrome Hereditar# alpha tr#ptasemia Seere mast cell mediated asthma Se ere anaph#la"is Indolent SM Indolent SM Smoldering SM Adanced SM Aggressie SM SM !ith an associated hematologic neoplasm Mast cell leukemia

 

 
 

 

P$a&&ed BLU-263 c$"&"ca$ +)"a$ a&d f,+,)e ('+e&+"a$ e/($')a+"'& BLU-263 (,&de) e-a$,a+"'&) AVAPRITINIB AVAPRITINIB AVAPRITINIB BLU-263 (+)"a$ ($a&&ed)* 66 * P$a& +' *,b%"+ IND a(($"ca+"'& "& 1H 2020 Ma*+ ce$$ d"*')de)* Ma*+ ce$$ ac+"-a+"'& *0&d)'%e He)ed"+a)0 a$(!a +)0(+a*e%"a Se-e)e %a*+ ce$$ %ed"a+ed a*+!%a Se-e)e a&a(!0$a/"* I&d'$e&+ SM I&d'$e&+ SM S%'$de)"& SM Ad-a&ced SM A)e**"-e SM SM ."+! a& a**'c"a+ed !e%a+'$' "c &e'($a*% Ma*+ ce$$ $e,#e%"a

 

 
 

 

Q & A

 

 
 

 

b r e a k

 

 
 

 

A prolific platform for precision medicine MARION DORSCH, PhD Chief Scientific Officer

 

 
 

 

Cancer is a genetic disease that evolves and becomes more elusive Cancer is a disease driven b enomic a errations Cancer evolves over time with new molecular chan es Tumors and their microenvironments are inherentlb complex 70

 

 
 

 

Bl&e"#i % Medici e$ i$ b&il% %! %ackle %he challe ge$ !f %#ea%i g ca ce# TRANSFORMATIVE BENEFIT URGENCY EFFICIENCY 71 * Re$ea#ch "!#%f!li! d#i'e b) "#!g#am$ (i%h high probability of success * Early go/no-go decisions (i%h a ga%ed, da%a-d#i'e !"e#a%ig m!del * S%#eamlied di$c!'e#) a""#!ach e abled b) a proprietary library * Integrated research capability %! #a"idl) ada"% %! e'!l'ig i$igh%$ * Deep biological knowledge %! ide%if) a#ea$ !f %#a$f!#ma%i'e "!%e%ial * Abili%) %! de$ig highly selective medicines agai $% challegi g "#!file$

 

 
 

 

A ,#&)%e, +e%#ab%e a'd +e)+(d.c#b%e a))+(ac" -( de,#!'#'! -a+!e-ed -"e+a)#e, 2 U'#*.e c(%%ec-#(' ( ,&a%% &(%ec.%e $#'a,e #'"#b#-(+, H#!"-*.a%#-1 c"e&#,-+1 ,-a+-#'! )(#'-, T((%, -( .'c(/e+ '(/e% -a+!e-, a'd b#(%(!1 2 Ne0 #',#!"-, #'-( -"e b#(%(!1 ( $#'a,e, a, d#,ea,e d+#/e+, Ide'-# #ca-#(' ( 'e0 d+.! -a+!e-, +(& K#'a,e, ( U'$'(0' B#(%(!1 (KUB,) 2 2 2 HIGH LY SELECTIVE AND POTENT KINASE INHIBITO R DRUG CANDID ATES K#'(&e #%%.,-+a-#(' +e)+(d.ced c(.+-e,1 ( Ce%% S#!'a%#'! Tec"'(%(!1, I'c. (000.ce%%,#!'a%.c(&) (CSTI). T"e (+e!(#'! 0eb,#-e #, &a#'-a#'ed b1 CSTI, a'd B%.e)+#'-Med#c#'e, #, '(-+e,)(',#b%e (+ #-, c('-e'-. 72

 

 
 

 

I30-#4' 3'-'%4+6' 34#24+/) 10+/43 7+4*+/ 052 12012+'4#28 %0.105/& -+$2#28 Broad and deep kinome coverage Rationally designed GG##4','''11''12'2 :S'-'%4+6+48; 10%,'4 96 3%#(( 0-&3 4-5 3%#(( 0-&3 1-3 3%#(( 0-&3 0 30-6'/4 <1% 06'2-#1 7+4* ?OM %0.105/&3 +/ P5$C*'. DESIGNED O BALANCE NO!EL ", PO ENC ", AND SELEC I!I " SCREENED A GAINS A LARGE PANEL OF KINASES I!E PROCESS I ERA K+/0.' +--5342#4+0/ 2'120&5%'& %0524'38 0( C'--S+)/#-+/) '%*/0-0)8, I/%. (777.%'--3+)/#-.%0.) (CS I). *' (02')0+/) 7'$3+4' +3 .#+/4#+/'& $8 CS I, #/& B-5'12+/4 M'&+%+/'3 +3 /04 2'310/3+$-' (02 +43 %0/4'/4. 73

 

 
 

 

Accelerate the disco!er" process b" shortening the time to lead identification TRADI TI O NAL A PPRO ACH BLUEPRI N T MEDI CI NES ' ACCELER ATED APPRO ACH Target Target Librar" Prioriti#ed Hits Target-Specific Screen e g , HTS, kinase-directed, str ct re-based design, fragment-based screen Lead Hits ./ ./ ./ ./ No target-specific screen needed Annotation "ields prioriti#ed hits Prioriti#ed Hits F ll nderstanding of selecti!it" Informed optimi#ation Lead HTS, high thro ghp t screen 74

 

 
 

 

Ref ne selec " # aga ns challeng ng arge s b# n egra ng da a PARALOGS WITH HIGH DEGREE OF SIMILARITY (DIFFERENCES SHOWN IN GREEN) BIOCHEM/ X-R AY MD/ FE P ATP BINDING POCKET $ $ $ $ S r!c !ral b o nforma cs Molec!lar D#nam cs (MD) Free Energ# Per !rba ons (FEP) Chem nforma cs 75 ATP, adenos ne r phospha e.

 

 
 

 

A closely integrated discovery model enables sustainable innovation APPROACH DETECT INTERPRET ACT 76 INTEGRATED DISCOVERY & DEVELOPMENT Cli ical Ne( P#!d&c% De'el!"me%Pla i 9

 

 
 

 

Cancer is a genetic disease that evolves and becomes more elusive Cancer is a disease driven b enomic a errations Cancer evolves over time with new molecular chan es Tumors and their microenvironments are inherentlb complex 77

 

 
 

 

Ra)$d%1 d*$. ,( ,*a'+!(*&a,$. (-,c(& + $' a*%1 c%$'$ca% , +,$'" ADVANCED SYSTEMIC MASTOCYTOSIS KIT D816V e#!ca" &%'e$c( ICS0 0.22 $M b!%c Ma0$&-& * d-c,$(' $' + *-& ,*1),a+ 1 PDGFRA D842-DRIVEN IST Cancer is a disease driven by genomic aberrations a.a)*$,$'$b PDGFRA D842V b!%ce#!ca" &%'e$c( ICS0 0.24 $M Ma0$&-& * d-c,$(' $' ,a*" , ,-&(*+2 K$'(& $%%-+,*a,$(' * )*(d-c d c(-*, +1 (! C %% S$"'a%$'" T c#'(%("1, I'c. (///.c %%+$"'a%.c(&) (CSTI). T# !(* "($'" / b+$, $+ &a$',a$' d b1 CSTI, a'd B%-)*$', M d$c$' + $+ '(, * +)('+$b% !(* $,+ c(', ',. 1. Da,a )* + ', d a, ,# E-*() a' H &a,(%("1 A++(c$a,$(' A''-a% M,$'" $' J-' 2019. Da,a c-,(!! da, : Ja'-a*1 2, 2019. 2. Da,a )* + ', d a, ASCO 2019 A''-a% M,$'" (' J-' 1, 2019. Da,a c-,(!! da, : N(. &b * 16, 2018. 78

 

 
 

 

Le)e%age c i"ica i"&igh'& '# e"ab e "e+' ge"e%a'i#" i"hibi'#%& EQUI ALENT POTENC" IMPRO ED SELECTI IT" LO!ER CNS PENETRATION BLU-263 B(,$'&*($#) -,.&+$0 (IC50, +M) Cancer is a disease driven by genomic aberrations D816 D842 BLU-263 0.2 0.3 0.1 A)a$%i'i"ib 0.22 0.24 0.1 Ki"#!e i (&'%a'i#" %e$%#d(ced c#(%'e&, #f Ce Sig"a i"g Tech"# #g,, I"c. (***.ce &ig"a .c#!) (CSTI). The f#%eg#i"g *eb&i'e 79 i& !ai"'ai"ed b, CSTI, a"d B (e$%i"' Medici"e& i& "#' %e&$#"&ib e f#% i'& c#"'e"'. C,*-,/+% KIT PDGFRA KIT 560G/D816

 

 
 

 

P edic" and p e$en" e!i!"ance p o!pec"i$el& MTC %a( e#( ) (h ge&"! #e RET V804M 150 100 50 0 C1D1 C5D1 C9D1 C13D1 C17D1 Cycle p al!e"inib O#g$ #g PR >19 "$#(h' Cancer evolves over time with new molecular changes 8 $che" ca! %$(e#c* (ICS0, #M) WT RET CCDC6-RET M918T RET V804L RET V804M 0.4 nM 0.4 nM 0.4 nM 0.3 nM 0.4 nM Kinome ill#!" a"ion ep od#ced co# "e!& of Cell Signaling Technolog&, Inc. (%%%.cell!ignal.com) (CSTI). The fo egoing %eb!i"e i! main"ained b& CSTI, and Bl#ep in" Medicine! i! no" e!pon!ible fo i"! con"en". PR, pa "ial e!pon!e. 80 Sum of Target Lesions (mm)

 

 
 

 

Navigate challenging target profiles to tackle tumor evolution EGFR+ NSCLC treatment paradigm Osimertinib 2L EGFR inhibitor Cancer evolves over time with new molecular changes CNS activit! 81 OPTIMAL PROFILE Potenc! against activating and resistance mutants Selectivit! over ild-t!pe EGFR Enabled for

 

 
 

 

ln"e oga"e mechani!m! "o iden"if% " an!fo ma"i$e combina"ion oppo "#ni"ie! CLINICAL PROOF-OF-CONCEPT DATA1 HUMANIZED PRECLINICAL MODEL Ac#i$i#% !f fi"!ga#i ib i FGF19+ HCC 100 PRE-TREATMENT 80 60 40 20 0 POST-TREATMENT WITH FISOGATINIB Tumors and their microenvironments are inherently complex -20 -40 lnc ea!ed T-cell infil" a"ion -60 -80 -100 82 1 Data presented at ILCA annual meeting in September 2017. Data cutoff date: August 18, 2017. Plan "o ini"ia"e combina"ion " ial of fi!oga"inib and CS"one&! an"i-POL1 CS-1001 in 04 2019

 

 
 

 

Harness the immune s stem to attack complex tumors MAP4K1 IS A NEGATIVE REGULATOR OF T-CELL FUNCTION ZAP?O Tumors and their microenvironments are inherently complex MAP4K1 83 Hernadez, et al. Cell Reports, 2018. Grb2 Gads

 

 
 

 

Bl&e"#i % Medici e$ i$ b&il% %! %ackle %he challe ge$ !f %#ea%i g ca ce# TRANSFORMATIVE BENEFIT URGENCY EFFICIENCY 84 * Re$ea#ch "!#%f!li! d#i'e b) "#!g#am$ (i%h high probability of success * Early go/no-go decisions (i%h a ga%ed, da%a-d#i'e !"e#a%ig m!del * S%#eamlied di$c!'e#) a""#!ach e abled b) a proprietary library * Integrated research capability %! #a"idl) ada"% %! e'!l'ig i$igh%$ * Deep biological knowledge %! ide%if) a#ea$ !f %#a$f!#ma%i'e "!%e%ial * Abili%) %! de$ig highly selective medicines agai $% challegi g "#!file$

 

 
 

 

Cont nued product v ty: planned research m lestones n 1H 2020 85

 

 
 

 

[LOGO]

 

 
 

 

Addressing tumor evolution in lung cancer TIM GUZI, PhD Senior Vice President, Chemistry L.O. v ng w th NSCLC

 

 
 

 

L4.( $".$&1 *2 " +*."2&-%1*5&. %*2&"2& 01*-&% '/1 3"1(&3&% 3)&1"08 IDENTIFIABLE ONCOGENIC DRIVERS1 EVOLVING NSCLC TESTING PARADIGM : 970-80% /' NSCLC 0"3*&.32 "1& 3&23&% '/1 EGFR ".% ALK ",3&1"3*/.2 : R&*-#412&-&.3 /' NGS 3&23*.( *2 *-01/5*.( (&.(., M&%*$"1& N"3*/.", C/5&1"(& D&3&1-*."3*/.) : P1&$&%&.3 &7*232 '/1 3&23*.( 0/23-01/(1&22*/. 6*3) /2*-&13*.*# 0,"2-"-#"2&% $/-0".*/. %*"(./23*$ : P,"2-"-#"2&% 3&23*.( 3&$)./,/(8 *2 *.$1&"2*.(,8 $/-0"1"#,& 3/ 3*224&-#"2&% 3&23*.( L NG CANCER REMAINS THE LEADIN G CA SE OF CANCER DE AT H GLOBAL L! 2 1 O.$/(&.*$ %1*5&12 *. ,4.( "%&./$"1$*./-". L4.( C".$&1 F/4.%"3*/. /' A-&1*$" 6&#2*3& (666.,$'"-&1*$"./1(). A$$&22&% O$3/#&1 27, 2019. 2 K&8 S3"3*23*$2 '/1 L4.( C".$&1. A-&1*$". C".$&1 S/$*&38 6&#2*3& (666.$".$&1./1(). A$$&22&% O$3/#&1 27, 2019. 88

 

 
 

 

T(!#% e)# ('i#" a"d 'h%ee a$$%#ache& f#% achie)i"g d(%ab e $a'ie"' be"efi' INITIAL ACTI VAT ING ONCOGENIC DRIVER INCREASING TUMOR MOLECULAR HETEROGENEITY SUR V I VAL OF RESIS TANT CLONES 89 1L TARGETED THERAPY Po enc# & selec i"i # essen ial for s!ccess COMBINATION SEQUENTIAL OPTIMIZED 1L

 

 
 

 

A closely integrated discovery model enables sustainable innovation APPROACH DETECT INTERPRET ACT 90 INTEGRATED DISCOVERY & DEVELOPMENT Cli ical Ne( P#!d&c% De'el!"me%Pla i 9

 

 
 

 

NSCLC 0"3*&.32 6*3) RET '42*/.2 )"5& ./ )*(),8 &''&$3*5& 31&"3-&.3 /03*/.2 Cabozantinib-resistant KIF58-RET(V804L) KIF58-RET &)*$,& QD $"#/9".3*.*# 60 -(/+( QD 01",2&3*.*# 01",2&3*.*# 01",2&3*.*# 3 -(/+( BID 10 -(/+( BID 30 -(/+( BID Pralsetinib: )*() +*./-& 2&,&$3*5*38 '/1 RET : : : : : Chemotherapy: ./.20&$*'*$, ,/6 1&20/.2& 1"3&2, 2*(.*'*$".3 3/7*$*38 Checkpoint inhibition: P1&,*-*."18 &5*%&.$& '/1 ,"$+ /' #&.&'*3 *. RET-",3&1&% NSCLC1 Multi-kinase inhibitors: < "$3*5*38, ; /''-3"1(&3 3/7*$*382,3 G1/6*.( 4.%&123".%*.( /' RET-%1*5&. 1&2*23".$& N/ 2&,&$3*5& RET *.)*#*3/12 "1& "001/5&% RET+ NSCLC K*./-& *,,4231"3*/. 1&01/%4$&% $/413&28 /' C&,, S*(.",*.( T&$)./,/(8 I.$. (666.$&,,2*(.",.$/-) (CSTI). T)& '/1&(/*.( 6&#2*3& *2 -"*.3"*.&% #8 CSTI, ".% B,4&01*.3 M&%*$*.&2 *2 ./3 1&20/.2*#,& '/1 *32 $/.3&.3. 1 M"9*&1&2, &3 ",. JCO 2018. 2 D1*,,/., &3 ",. L".$&3 2017. 3 !/), &3 ",. L".$&3 R&20*1 M&% 2017. 91

 

 
 

 

P%#!i&i"g da'a &($$#%'i"g $%a &e'i"ib i" RET+ NSCLC Gainor, et al. ASCO, 2019. 92 Da'a $%e&e"'ed a' ASCO A""(a Mee'i"g i" J("e 2019. Da'a c('#ff da'e: A$%i 28, 2019.

 

 
 

 

E%idence of d$!able CNS ac#i%i#' &i#h !al"e#inib Evans, et al. IASLC, 2019. 93 Da#a !e"en#ed a# IASLC Wo!ld Confe!ence on L$ng Cance! in Se #embe! 2019. Da#a c$#off da#e: A$g$"# 16, 2019.

 

 
 

 

Case reports h gh ght the potent a for comb nat on therap! th pra set n b Piotrowska, et al. IASLC, 2018. 94 Data presented at IASLC Wor d Conference on Lung Cancer n September 2018.

 

 
 

 

P(a#)e*!%!b !) a '&*e%*!a# be)*-!%-c#a)) )e#ec*!,e RET !% c&(%e()*&%e &f &+( #+%g ca%ce( '&(*f&#!& !b!*&( a%d * e EQUIPOTENT INHIBITION &f RET f+)!&%) a%d $+*a*!&%), !%c#+d!%g '(ed!c*ed ga*e"ee'e( (e)!)*a%ce $+*a*!&%) CLINICAL RESPONSES !% 2 &f 4 'a*!e%*) '(e,!&+)#. 1 *(ea*ed -!* )e#'e(ca*!%!b HIGH RESPONSE RATES AND DURABLE ACTIVITY !% NSCLC a%d MTC 'a*!e%*)1 FDA BREAKTHROUGH THERAPY DESIGNATIONS f&( NSCLC a%d MTC STRONG ACTIVITY AGAINST BRAIN METASTASES !% 'a*!e%*) -!* NSCLC1 WELL-TOLERATED WITH LOW DISCONTINUATION RATES !% ad,a%ced ca%ce( '&'+#a*!&%)1 95 1. Da*a '(e)e%*ed a* ASCO A%%+a# Mee*!%g !% J+%e 2019. Da*a c+*&ff da*e: A'(!# 28, 2019.

 

 
 

 

A ., #* - 0, 0. +/%,.* +"$ *10 0(2$ !$+$%(0 !4 0 0(,+/ .&$0(+& 0'$ -.(* .4 #.(2$. +# -.$#("0$# .$/(/0 PRALSETINIB RET +)#&%+ NSCLC ()*a(*#%! d&)e 400 $! QD) OSIMERTINIB EGFR+ T790M NSCLC '(#&( ),)*e$#c *"e(a',2 1 40 20 0 -20 -40 -60 P) 0(+1*-+(2$ -80 -100 1 D 0 -.$/$+0$# 0 ASCO A++1 ) M$$0(+& (+ J1+$ 2019. I+")1#$/ NSCLC - +# $+.,))$# / ,% N,2$*!$. 14, 2018 3(0' %,)),3-1-0'.,1&' # 0 "10,%% # 1643-1652DOI (10.1016/S1470-2045(16)30508-3). 0($+0/ 0.$ 0$# 0 0'$ .$",**$+#$# P' /$ 2 #,/$ ,% 400 *& QD 0$ ,% A-.() 28, 2019. *, *,+0'/. 2 T'$ L +"$0 O+",),&4 2016 17, 96 P.(,. P) 0(+1*

 

 
 

 

E& *"$'" da,a +#(-)(, ',$a% * a,& +$+,a'c )*(!$% + !(%%(-$'" !$*+,-%$' a'd + c('d-%$' (+$& *,$'$b ,* ', $' EGFR+ NSCLC + C797S + T790M a'd C797S E.(' 19/L858R T790M C797S C797S EGFR+ CS TMCS ONCOGENIC DRIVER FOLLOWING 1L OSIMERTINIB FOLLOWING 2L OSIMERTINIB 98

 

 
 

 

E& *"$'" da,a +#(-)(, ',$a% * a,& +$+,a'c )*(!$% + !(%%(-$'" !$*+,-%$' a'd + c('d-%$' (+$& *,$'$b ,* ', $' EGFR+ NSCLC + C797S + T790M a'd C797S E.(' 19/L858R T790M C797S C797S EGFR+ CS TMCS ONCOGENIC DRIVER FOLLOWING 1L OSIMERTINIB FOLLOWING 2L OSIMERTINIB 98

 

 
 

 

O&# ' $ ! : !"% m )ed EGFR+ %#ea%me % #ega#d e$$ !f "# !# %he#a"( T790M C797S 1$% ge e#a% ! EGFR TKI O$ me#% b Blueprint EGFR+ LRTMCS TKI, %(#!$ e k a$e h b %!#. 99

 

 
 

 

BLU4810 i& a $#'e"' a"d &e ec'i)e EGFR+ TMCS i"hibi'#% POTENT AGAINST RESISTANT EGFR MUTANTS AND >IC90 COVERAGE FOR 12 HOURS SELECTIVE OVER ILD-T!PE ( T) EGFR B L U 4 8 1 0 b i o c h e m I C 50 8 L U 4 8 1 0 P K P D e l a " i o n ! h i p 150 W T 100 %"*&" = 1.3 'M L R T M C S 100 Δ E X 1 9 T M C S L R T M 50 0 1 1 0 1 00 1000 10000 0 P l a ! m a P K 0. 01 0. 1 1 10 1001 000 10000 [ B L U 4 8 1 0 ] (n M ) 100 mg/kg, B D veh cle , , , P#'e"' agai"&' d#(b e a"d '%i$ e EGFR %e&i&'a"' !('a"'& High + &e ec'i)e #)e% *i d-'+$e EGFR R#b(&' i" )i)# g%#*'h i"hibi'i#" c#!$a%ab e '# #&i!e%'i"ib 2 hr 6 hr 12 hr 2hr $EGFR $ERK GAPDH 100 % i n h i b i t i o n p - E G F R I G A P D H n o m a l i $ e d " o # e h i c l e U'#(+'$ ) )EGFR ICS0

 

 

 

 

BLU4810 # a ! $en$ and #elec$ &e EGFR+ TMCS nh b $ " POTENT AGAINST RESISTANT EGFR MUTANTS AND SELECTIVE OVER WILD-TYPE (WT) EGFR TUMOR GROWTH INHIBITION IN EGFR+TM CDX MODEL 1000 B L U 4 8 1 0 b i o c h e m I C 50 W T 100 L R T M C S Δ E X 1 9 T M C S L R T M 50 500 0 0. 01 0. 1 1 10 100 1 000 10000 [ B L U 4 8 1 0 ] (n M ) ) ) ) P $en$ aga n#$ d %ble and $" !le EGFR "e# #$an$ m%$an$# &e" ' ld-$(!e EGFR H ghl( #elec$ &e 0 0 5 10 15 R b%#$ n & & g" '$h nh b $ n c m!a"able $ # me"$ n b D a y s a f t e r r a n d o m i z a t i o n 101 % i n h i b i t i o n 3 H 1 9 7 5 T u m o r V o l u m e [ m m ] M e a n S E M V e h i c l e 8 L U 4 8 1 0 , 1 00 m g / k g 8 I 0 0 s i m e r ti n i b , 5 m g / k g Q 0

 

 
 

 

Anti-tumor acti it" in a EGFR+ TMCS patient-deri ed tumor model PDX MODEL RESISTANT TO ERLOTINIB AND OSIMERTINIB TUMOR REGRESSION WITH 1OO MG/KG BID DOSING OF BLU481O B 0 0 3 0 0 0 0 2 0 0 4 0 0 1 0 0 2 0 0 0 0 0 5 1 0 1 5 2 0 2 5 0 5 1 0 1 5 2 0 2 5 D a y s a f t e r r a n d o m i z a t i o n D a ! s a f t e r r a n d o m i " a t i o n EGFR+ TMCS model from a patient !ho !ent through se en lines of therap", including chemotherap", erlotinib and osimertinib 102 3 P D X T m o r V o l m e [ m m ] M e a n # S E M 3 P D X T u m o r V o l u m e [ m m ] M e a n S E M V e h c e B L U 4 8 1 0 1 0 0 m g / k g B D V e h c e E r o t n b 5 0 m g /k g Q 0 0 s m e r t n b 5 m g / k g Q 0 E r o t n b + 0 s m e r t n b

 

 
 

 

Our vision: optimi ed EGFR+ treatment regardless of prior therapy C797S Osimertinib Blueprint EGFR+ CS 103

 

 
 

 

EGFR+ CS series are potent, selecti e and brain penetrant 125 100 75 7650 EGFR+ b EGFR+ 650 WT b WT 50 25 0 0.01 1 100 10000 1000000 C"!ce!$#a$ "! (!M) $ $ Lead series sho! fa orable properties required for a best-in-class target product profile Preliminar# e"amples sho! good brain penetration 104 % 1!h b $ "! BLU Gef $ ! BLU7 Gef $ ! Biochemical assa Cellular assa EGFR-"IC)%! nM# Selectivit over WT EGFR-"IC)%! nM# WT "IC)%! nM# Selectivit over WT Gefitinib 0.8 6x 1 10 10x Erlotinib 0.6 9x 4 85 3x Osimertinib 4 13x 3 139 5 x BLU+*)% "Series &# 0.7 50x 1 87 73x BLU)*(, "Series '# 0x 6 4 6 71x

 

 
 

 

Our vision: optimi ed EGFR+ treatment regardless of prior therapy 1st generation EGFR TKI Osimertinib Blueprint EGFR+ TMCS Osimertinib Blueprint EGFR+ CS Osimertinib Blueprint EGFR+ CS Blueprint EGFR+ TMCS TRANSFO RM AT I V E PREVENTIVE C O MB IN AT ION 105

 

 
 

 

We aim to bring our approach to delivering durable benefit to additional patient populations Durability Patient selection Tumor evolution HIGHLY SELECTIVE INHIBITORS Potent inhibition of genetic drivers leads to rapid and deep responses BIOMARKER DRIVEN ADAPTIVE ABILITY Research engine rapidly empowers solutions for acquired resistance Understanding of disease heterogeneity enables responder hypotheses 106

 

 
 

 

Cancer immunotherapy: a new frontier for kinase medicines KLAUS HOEFLICH, PhD Vi ce President, Biology

 

 
 

 

T'% (+.!#1 -& #!,#%/ (++2,-1'%/!.4 0.!,0 0%3%/!* $(&&%/%,1 1/%!1+%,1 +-$!*(1(%0 !,$ ! "/%!$1' -& (,$(#!1(-,0 APPROVED CANCER IMMUNOTHERAPIES BY MECHANISM AND CANCER TYPE 14 Latest Appro al ? 5 5 4 2 2 2 2 2 1 1 2010 (P/-01!1%) 3!##(,%0 C'%#).-(,1 (,'("(1-/0 C41-)(,%0 P/%3%,1(3% 3!##(,%0 T'%/!.%21(# 3!##(,%0 CAR-T O,#-*41(# 3(/20 C!,#%/ 14.%0 TO D AT E, NO SMALL MOLECULE CANCER IMMUNOTHERAPIES ARE APP R O E 108 Modalit!1st approal / C'%#).-(,1 2011 (M%*!,-+!) I (,'("(1-/0 2019 (B/%!01) C41-)(,%01992 (K($,%4) I 2011 (M%*!,-+!) P/%3%,1(3% 2009 (C%/3(#!* #!,#%/) I 3!##(,%02014 (3!/(-20) T'%/!.%21(# CAR-T201? (ALL) I 2018 (L4+.'-+!) O,#-*41(# (/202015 (M%*!,-+!)

 

 
 

 

Kinase inhibition: A new approach to affecting anti-tumor immune response • Most immunotherapies today are biologics targeting surface targets • Targeting intracellular targets with selective small molecule inhibitors: - - Promotes exploration of novel modes of action Enhances opportunities for combinations with tumor-targeted agents and biologic immunotherapies Intracellular Target Opportunity • Targeting kinases to enhance immune response against cancer is an emerging field 109

 

 
 

 

Cancer immunotherapy complements our precision medicine strategy Kill tumor cells Activate the immune system M8 Turn off drivers Sensitize to immune attack Tumor detection Tumor killing 110

 

 
 

 

A )*(a*eg!c c&##ab&(a*!&% *& *(a%)f&($ * e f!e#d &f ca%ce( !$$+%&* e(a'/ R&b+)* "!%a)e (e)ea(c Ca%ce( !$$+%&* e(a'/ '#a*f&($ a%d de,e#&'$e%* ca'ab!#!*!e) e.'e(*!)e, a))e*) a%d !%f(a)*(+c*+(e 2016: EXPLORE COMPELLING TARGETS 2019: PROGRESS TOWARDS THE CLINIC 1 Goal: E.'#&(e a (a%ge &f !$$+%&"!%a)e *a(ge*) *& ad,a%ce ca%ce( !$$+%&*e(a'/ 1 Achieved: 4 *a(ge*) )e#ec*ed f&c+)!%g &% d!)*!%c* a%d c&$'#e$e%*a(/ !$$+%e $ec a%!)$) 1 1 I$$ed!a*e#/ ac*!&%ab#e N&,e# ,!a ce##-ba)ed 'e%&*/'!c )c(ee%) 1 1 1 1 Ac*!,a*e effec*&( ce##) P(!$e !$$+%e (e)'&%)e T+$&( ce## "!##!%g P(e,e%* e,a)!&% f(&$ !$$+%e de*ec*!&% 1 I%*e((&ga*e a%d ,a#!da*e -!* ge%e*!c a%d *&&# c&$'&+%d a''(&ac e) B#+e'(!%* Med!c!%e) a) U.S. c&$$e(c!a# (!g *) f&( +' *& *-& '(&g(a$). R&c e a) -&(#d-!de c&$$e(c!a#!0a*!&% (!g *) f&( +' 111 *& *-& '(&g(a$) a%d e.-U.S. c&$$e(c!a#!0a*!&% (!g *) f&( +' *& *-& '(&g(a$).

 

 
 

 

N,2#) /!.##+/ '"#+0'$5 a!0',+a )# ('+a/# 0a.%#0/ $,. !a+!#. '**1+,0&#.a-5 0 Ca/9 !,+0.,) 0 K'+a/# KO LITERATURE B)1#: C,2#.#" ('+a/#/. R#": K'+a/#/ +,0 !,2#.#" B)1#-.'+0 0,,) !,*-,1+" /#0 IO $1+!0',+a) /!.##+/ T1*,.-T !#)) !,-!1)01.# /!.##+/ T !#)) #4&a1/0',+ /!.##+ A+0'%#+ -.#/#+0a0',+ #+&a+!#*#+0 /!.##+ Ta.%#0 "#!,+2,)10',+ Ta.%#0 2a)'"a0',+ TWO KINASE DISCOVERY PROGRAMS H AVE ORIGIN AT ED FROM CELL-BASED PHENOTYPIC SCREEN S WITHIN T HE ROCHE COLLA B O R AT I O N K'+,*# '))1/0.a0',+ .#-.,"1!#" !,1.0#/5 ,$ C#)) S'%+a)'+% T#!&+,),%5, I+!. (333.!#))/'%+a).!,*)(CSTI). T&# $,.#%,'+% 3# /'0# '/ *a'+0a'+#" 5 CSTI a+" B)1#-.'+0 M#"'!'+#/ '/ +,0 .#/-,+/' )# $,. '0/ !,+0#+0. C-"; !,*-,1+"; DMSO, "'*#0&5) /1)$,4'"#; IO, '**1+,0&#.a-5; TCB, T-!#)) '/-#!'$'! a+0' ,"5 112 T1*,. K'))'+%

 

 
 

 

Our scientific platform enables us to e!plore ne kinase biolog", iNNO VATiON representing even larger opportunities to impact patient care immunokinase inhibitor 113 MAP4K1 is a collaboration target under the cancer immunotherap" collaboration ith Roche.

 

 
 

 

MAP4K1 +3 # /')#4+6' 2')5-#402 0( " %'--(5/%4+0/ TCR Ac( *a( $# Rec&) ("e#( A((e#)a( $# CD3 CD4 SP S376 LCK MAP4K1 SLP-76 SLP-76 ZAP70 SLP-76 PLCγ DAG+IP3 IL-2, IFNγ, %&$! fe&a( $# AP-1 NF-κB NF-AT Ge#e (&a#'c& %( $# 9 9 9 M AP4K1 +3 # !E /"H ,+/#3' 3'-'%4+6'-8 '712'33'& +/ DC3, "-#/& B-%'--3 N ')#4+6'-8 2')5-#4'3 "C #/& BC 3+)/#-+/), DC .#452#4+0/ M AP4K1 -/-02 MAP4K1 KD/ K D .+%' '7*+$+4 '/*#/%'& 45.02 +..5/+48 J. E71. M'&. (2007) 2004: 681-91. C#/%'2 l..5/0-l..5/04*'2 (2010) 59: 419-29. C'--'10243 2018; 25(1):80-94. BC , B %'--2'%'1402; DC, &'/&2+4+% %'--; l0, +..5/04*'2#18; !'2, 3'2+/'; "C , " %'--2'%'1402; "*2, 4*2'0/+/'. 114 LAT LAT 14-3-3 LAT

 

 
 

 

O)& %!a(f$&" ha' e#ab!ed de'ig# $f %$(e#( a#d 'e!ec(i*e MAP4K1 i#hibi($&' H u m a n T ceI I s 15000 10000 5000 0 0 1 0 3 0 100 300 c o m p ou n d c on c e nt r a t i on ( nM ) C03/28 stimulated M)!(i%!e !ead 'e&ie' ide#(ified di&ec(!-f&$" $)& !ib&a&-S(&)c()&a! i#'igh(' a#d i#a'e e,%e&(i'e ($ $%(i"i.e f$& %$(e#c-a#d 'e!ec(i*i(-Dee% a#d '-'(e"a(ic bi$!$g-i#(e&&$ga(i$# )#c$*e&ed e-$ff-(a&ge( i#'igh(' ()#di'c!$'ed) Mi#i"a! $ff-(a&ge( ac(i*i(-R$b)'( T ce!! ac(i*a(i$# / / / S )b-#a#$"$!a& %$(e#c-f$& MAP4K1 100-1000, 'e!ec(i*i(-f$& MAP4K1 *'. a#(i-(a&ge(' F a*$&ab!e %ha&"ac$i#e(ic a#d %h-'ic$che"ica! %&$%e&(ie' Ki#$"e i!!)'(&a(i$# &e%&$d)ced c$)&(e'-$f Ce!! Sig#a!i#g Tech#$!$g-, I#c. (+++.ce!!'ig#a!.c$")(CSTI). The f$&eg$i#g +eb'i(e i' "ai#(ai#ed b-CSTI a#d B!)e%&i#( Medici#e' i' #$( &e'%$#'ib!e f$& i(' c$#(e#(. 115 I L - 2 ( p g l m I)

 

 
 

 

MAP4K1 e!hibits immune-dependent anti-tumor activit" in multiple s"ngeneic models via an immune-dependent mechanism MOUSE COLON MOUSE SARCOMA l m u n o c o m p r o m i s e d m i c e 1 5 0 0 1 5 0 0 8 0 0 1 0 0 0 6 0 0 1 0 0 0 4 0 0 5 0 0 5 0 0 2 0 0 0 0 5 1 0 1 5 0 5 1 0 1 5 8 1 0 1 4 D y s 1 6 1 8 d a y a f t e r r a n d o m i z a t i o n d a y s a f t e r r a n d o m i z a t i o n Ve h i c e Ve h i c e 8 L U 2 06 9 10 m g / k g 8 0 8 L U 2 06 9 10 m g / k g 8 0 An t i - P 0 L 1 1 0 m g / k g An t i - P 0 L 1 1 0 m g / k g 8 L U 2 069 1 0m g / k g 8 0 + A nt i-P 0 L1 8 L U 2069 10m g/ k g 8 0 + A nt i-P 0 L1 116 8 0 t ice dail" dosing. T u m o r V o l u m e [ m m 3 ] M e a n ± S E M T u m o r V o l u m e [ m m 3 ] M a n ± S E M T u m o r V o Iu m e [ m 3 ] M e a n ± S E M

 

 
 

 

MAP4K1 "&!"b","'& e&!a&ce+ T ce$$+ *e+('&+e+ a&d c/,'#"&e+ Ke/ f"&d"& + ** I&c*ea+ed f*e)-e&c/ 'f CDB+ TILS .",! +"& 0 0 0 $e a e&, ,*ea,%e&, E&!a&ced c/,'#"&e+ "& ($a+%a 'f c'%b' ,*ea,ed %"ce I%%-&e-(!e&',/(e "+ "& $"&e .",! MAP4K1 KI %'-+e * ** ** Treatment BLU2069 Ve!"c$e 117 Flow cytometry analysis of tumor infiltrating lymphocytes

 

 
 

 

MAP4K1 nh b t on nduces stronger tumor T cell responses than ant -PO-L1 Differen ial e"pression (BLU2069/!ehicle) Differen ial e"pression (An i-PD-L1/!ehicle) Differen iall# e"pressed gene o!erlap Ad usted p::0 05 Ad usted p::0 05 Log2 (fold change in gene e"pression) Log2 (fold change in gene e"pression) Significantly differentially expressed genes in red 118 -Log10 (P adj) -Log10 (P adj)

 

 
 

 

MAP4K1 $(c+ a, , c2-)%$( *+)d.c-$)( !+)' b)-# b&))d a(d -.')+ $(!$&-+a-$(" &2'*#)c2-, d +$/ d !+)' &.(" ad ()ca+c$()'a *a-$ (-IFN production PBMC FN-y product on T L1 800 T.')+ & b&))d c)&&c-d !+)' &.(" ca(c+ *a-$(-800 600 600 400 400 200 200 T.')+ d$,,)c$a-d $(-) a ,$("& c&& ,.,*(,$)( a(d PBMC, 0 0 $,)&a-d !+)' -# b&))d D$,,)c$a-c.&-.+d d TIL, a(d PBMC, 1 /$/) !)+ 24 #).+, IL 2 production PBMC IL 2 production TIL1 0$-# a(-$-CD3/CD28 ,-$'.&a-$)( +/-MAP4K1 $(#$b$-)+ 800 150 600 100 400 50 C2-)%$(, 'a,.+d $( -# c.&-.+ ,.*+(a-a(-, b2 MSD 200 0 0 119 1 TIL, -.')+ $(!$&-+a-$(" &2'*#)c2-,. 2 CD3/28 ,-$'.&a-d. PBMC, * +$*# +a& b&))d ')()(.c& a+ c &&,. IFN-3 (*"/'&) IL-2 (*"/'&) IL-2 (*"/'&) IFN-3 (*"/'&) basal 3nM 10nM 30nM 100nM 2 stimulated basa 3nM 10nM 30nM 100nM 2 stimu ated - basal - 3nM 10nM 30nM 100nM st mulated2 basa 3nM 10nM 30nM 100nM 2 stimu ated

 

 
 

 

Uniq"e and di#er e por!folio of no#el cancer imm"no!herap% !arge! & MAP4K1 pa!h !o de#elopmen! candida!e i repre en!a!i#e of !he broader "ndi clo ed cancer imm"no!herap% por!folio "nder !he Roche collabora!ion ► Plan !o nomina!e po!en!ial fir candida!e in 1H 2020 !-in-cla MAP4K1 de#elopmen! & Collabora!ion ha con!rib"!ed !o !he di#er ifica!ion and e$pan ion of Bl"eprin! Medicine ' por!folio deri#ed from o"r pla!form 120 Confiden!ial

 

 
 

 

O+*$&&# &( *!e +*+(e HIGH SUCCESS RATE - EFFICIENCY - PLATFORM EXPANSION 121 GIST 'a*"e%* ,")"* @ B$+e'("%* Med"c"%e), 2019.

 

 
 

 

Q & A

 

 
 

 

Jeff Albers r e m a r k s Chief Executive Officer

 

 
 

 

#-.5* 48'57+5 2019 ,.1'1).'/ 5+68/76 BA"ED ON C$!!EN# O E! A# ING LAN", E& EC# E&I"#ING CA"H BALANCE %ILL F$ND O E! A# ION" IN#O # HE "ECO ND HAL F O F 2 0 2 1 * * * $1'8*.7+* ** I1)/8*+6 $25.0 0.//.21 83,5217 )'6-3';0+17 ,520 C/+0+17.' '1* $8.0 0.//.21 5+6+'5)-0./+6721+ ')-.+9+* .1 7-+ ,2857-48'57+5 2, 2019 81*+5 7-+ !2)-+ )2//'(25'7.21 (87 +:)/8*+6 '1; '**.7.21'/ 327+17.'/ 237.21 ,++6, 0./+6721+ 3';0+176 25 27-+5 3';0+176 ,520 !2)-+, C"721+ 25 C/+0+17.'. 124 Three Mon hs Ended Sep ember 30, 2019* 2018* $9.1M $1.1M $81.5M $64.6M $25.6M $12.0M $(94.3)M $(72.7)M S a emen of Opera ions C2//'(25'7.21 !+9+18+ !+6+'5)-& D+9+/230+17 E:3+16+6 G+1+5'/ & A*0.1.675'7.9+ E:3+16+6 N+7 L266 Sep ember 30, 2019* December 31, 2018 $594.5M $494.0M Balance Shee C'6-, C'6-E48.9'/+176 '1* I19+670+176

 

 

 

 

 

 

We a!e $!"$ ng a h gh & a##!ac# %e "e# of o o!#$n # e" ac!o"" o$! o!#fo o GIST Opportunity SM Opportunity RET Opportunity NSCLC M0TC O#he! #$mo!" PDGFRA 4aL 3L 2L Ad%anced SM Indo en# SM 125 Figures are illustrative.

 

 

 

 

 

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

 

 

 

 

 

thank you