Charting the path from pioneering biology to impactful therapeutics

Q1 2019

NASDAQ: SRRA

S A F E H A R B O R S TAT E M E N TExcept for statements of historical fact, any information contained in this presentation may be a forward-lookingstatement that reflects the Company’s current views about future events and are subject to risks, uncertainties,assumptions and changes in circumstances that may cause events or the Company’s actual activities or results todiffer significantly from those expressed in any forward-looking statement. In some cases, you can identifyforward-looking statements by terminology such as “may”, “will”, “should”, “plan”, “predict”, “expect,” “estimate,”“anticipate,” “intend,” “goal,” “strategy,” “believe,” and similar expressions and variations thereof. Forward-lookingstatements may include statements regarding the Company’s business strategy, cash flows and funding status,potential growth opportunities, preclinical and clinical development activities, the timing and results of preclinicalresearch, clinical trials and potential regulatory approval and commercialization of product candidates. Althoughthe Company believes that the expectations reflected in such forward-looking statements are reasonable, theCompany cannot guarantee future events, results, actions, levels of activity, performance or achievements. Theseforward-looking statements are subject to a number of risks, uncertainties and assumptions, including thosedescribed under the heading “Risk Factors” in documents the Company has filed with the SEC. These forward-looking statements speak only as of the date of this presentation and the Company undertakes no obligation torevise or update any forward-looking statements to reflect events or circumstances after the date hereof.

Certain information contained in this presentation may be derived from information provided by industry sources.The Company believes such information is accurate and that the sources from which it has been obtained arereliable. However, the Company cannot guarantee the accuracy of, and has not independently verified, suchinformation.

T R A D E M A R K S :

The trademarks included herein are the property of the owners thereof and are used for reference purposes only.Such use should not be construed as an endorsement of such products.

Addressing Unmet Medical Needs with a Broad Pipeline

momelotinibTARGETING JAK1/2 AND ACVR1

THERAPEUTIC FOCUS

Myelofibrosis

SRA737TARGETING Chk1

THERAPEUTIC FOCUS

High Grade Serous Ovarian Cancer

Squamous Cell Carcinoma & Other Solid Tumors

SRA141TARGETING Cdc7

THERAPEUTIC FOCUS

Colorectal Cancer

DDR Network Programs

3

Our Pipeline of Targeted TherapeuticsPreclinical Phase 1 Phase 2 Phase 3 Focus

SIMPLIFY-1

SIMPLIFY-2

Additional Registration Study

Myelofibrosis

M O M E L O T I N I B

Preclinical Phase 1 Phase 2 Phase 3 Focus

SRA737-01 Monotherapy

SRA737-02 LDG Combination

PARP Inhibitor Combination

I/O Combination

S R A 7 3 7

Preclinical Phase 1 Phase 2 Phase 3 Focus

Monotherapy

S R A 1 4 1

High Grade Serous Ovarian

Prostate

Colorectal

4

Myelofibrosis

Myelofibrosis

Solid Tumors

High Grade Serous Ovarian

MOMELOTINIBTarget ing JAK1, JAK2 and ACVR1

6

MOMELOTINIBUniquely positioned to provide robust benefits in myelofibrosis: spleen, symptoms and anemia

>20 studiesPhase 1, 2 and 3

>1,200 peopledosed with momelotinib

>550 patientswith myelofibrosis treated

>7 yearson treatment for several patients

Momelotinib Potentially Addresses Key Needs in Myelofibrosis Treatment

7

Opportunity2nd-line myelofibrosis = anemic and

transfusion dependent; large unmet need with no approved therapies

BenefitOnly agent to impact all three myelofibrosis

hallmarks: anemia, enlarged spleen and constitutional symptoms

Robust DataTwo Phase 3 SIMPLIFY studies

support efficacy profile

RegistrationTotality of data supports potential path to

registration; strong KOL support for momelotinib

MyelofibrosisA Chronic Myeloproliferative Neoplasm (MPN)

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• Chronic, progressive myeloid cancer • Bone marrow disorder disrupting the body’s normal

production of blood cells• Leads to fibrosis of bone marrow limiting blood cell

production

CONSTITUTIONAL SYMPTOMS

SPLENOMEGALY

ANEMIA

Myelofibrosis

Inflammation

Inefficient hematopoiesis

Extramedullary hematopoiesis

The Three Hallmarks of a Progressive Disease

Tefferi A, et al. Mayo Clin Proc. 2012 9

Three Hallmarks of a Progressive Disease

> 1 Y E A R A F T E R D I A G N O S I S

CONSTITUTIONAL SYMPTOMSAnemia, chronic inflammation, and splenomegaly lead to constitutional symptoms

ANEMIAProgressive bone marrow fibrosis due to inflammation; decreased erythropoiesis

45% Transfusion Dependent

64%46%34%

MyelofibrosisThe Challenge of Anemia

“Anemia is major area of unmet need. That’s one of the major problems… a quarter of the patients at the beginning may require transfusions, and after one year of therapy almost half of the patients already require transfusion. Anemia and transfusion dependency are important prognostic factors.”

Srdan Verstovsek, MD, PhDProfessor in the Department of Leukemia at

The University of Texas MD Anderson Cancer Center, Houston

Unmet Medical Needs In Myelofibrosis; company conference call October 2018

SPLENOMEGALYExtramedullary hematopoiesis in the spleen and other organs

Myelofibrosis: More Treatment Options Needed

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• Only one agent approved: ruxolitinib(Jakafi®) for 1st-line myelofibrosis

• Ruxolitinib:• Addresses ~70% 1st-line patients• Projected global market: >$2B• Only treats spleen and symptoms

Anemia is not addressed by ruxolitinib

I N I T I A L T R E AT M E N T:

• Optimal myelofibrosis therapeutic would address all three hallmarks:

• Anemia and transfusion dependency • Splenomegaly• Constitutional symptoms

Physicians need more choices after ruxolitinib

U N M E T M E D I C A L N E E D S :

T R E AT I N G A N E M I A A N D T R A N S F U S I O N D E P E N D E N C Y R E M A I N S I G N I F I C A N T U N M E T M E D I C A L N E E D S

MOMELOTINIBAddresses all Three Hallmarks of Myelofibrosis

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INHIBITSACVR1

INHIBITSJAK2

INHIBITSJAK1

ANEMIA• Hepcidin impaired erythropoiesis

SPLENOMEGALY• JAK-STAT-driven clonal

myeloproliferation

CONSTITUTIONAL SYMPTOMS• Aberrant cytokine production

and immune dysregulation

AnemiaCritical Prognostic Factor in Myelofibrosis

Nicolosi et al; Leukemia 2018 12

Baseline Anemia:Mild = Hgb ≥ 10 g/dl but below lower limit of normalModerate = Hgb between 8 g/dl and <10 g/dlSevere = Hgb <8 g/dl or transfusion dependent

No anemia Median survival 7.9 years

Mild anemia Median survival 4.9 years

Moderate anemia Median survival 3.4 years

Severe anemia Median survival 2.1 years

Surv

ival

Years

0

0

2

4

6

8

10

5 10 15 20 25 30 35

P<0.0001

Multiple Pathways to Anemia in Myelofibrosis

13

BONE MARROW FIBROSIS INFLAMMATION JAK THERAPYHEPCIDIN

Displacement of marrow erythropoietic tissue by fibrosis

Extramedullary hematopoiesis and splenomegaly

Pro-inflammatory cytokine profile

ANEMIA

Inadequate extramedullary erythropoiesis and red blood cell

sequestration

Impaired erythroiddifferentiation

JAK inhibitor therapy induced

myelosuppression

Impairment of iron metabolism

Elevated hepcidin

Activated ACVR1Alterations in

bone marrow cytokine expression

Momelotinib Mechanism of Action: Reducing Hepcidin Restores Red Blood Cell Production

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P L A S M A I R O N D E F I C I E N C Y

Fe2+

Hepcidin

Erythroblast Precursors

Hgb Accumulation Reticulocytes RBCs

Momelotinib-mediated plasma iron elevation leads to stimulation of erythropoiesis and red blood cell production

P L A S M A I R O N N O R M A L I Z AT I O N

Hepcidin

Fe2+

The KOL View on Myelofibrosis

15

Thoughts from:

Srdan Verstovsek, MD, PhDProfessor in the Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston

Unmet Medical Needs In Myelofibrosis KOL Presentation, October 17, 2018; ASH Analyst Call, December 3, 2018

“Ruxolitinib may control the signs and symptoms of the disease for some time… but it doesn’t prevent progression.”

“The leading cause of loss of response that has been published is anemia.”

“Three quarters of the patients would be candidates… for a second line therapy.”

“The majority of patients…need another agent to salvage their quality of life, to control spleen, symptoms, and to improve the anemia, if possible.”

“Momelotinib… unlike any other JAK inhibitor, can benefit patients to a great extent on all three aspects.”

Completed Phase 3 Studies with Momelotinib

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1st-Line Population: Previously untreated with JAKi

SIMPLIFY-1

JAK NaïveDouble-blind,

N=432

Momelotinib 200 mg QD

Ruxolitinib20 mg BID

Momelotinib 200 mg QD

1:1

rand

omiz

atio

n

Double-blind treatment Open label LTFU

Year 7Day 1 Week 24

Primary Endpoint

Goal: Non-Inferiority

MMB: N=215

RUX: N=217

Primary Endpoint Splenic Response Rate

Secondary Endpoints • Total Symptom Score• Effects on red blood cell

transfusion requirements

Goal: Superiority

MMB: N=104

RUX: N=52

Primary Endpoint Splenic Response Rate

Secondary Endpoints • Total Symptom Score• Effects on red blood cell

transfusion requirements

2nd-Line Population: Anemic or thrombocytopenic subjects previously treated with ruxolitinib

SIMPLIFY-2

JAK ExposedOpen label,

N=156Momelotinib 200 mg QD Momelotinib

200 mg QD

2:1

rand

omiz

atio

n

Randomized treatment Extension LTFU

Year 7Day 1 Week 24

Primary Endpoint

90% = RUX/RUX+

Best available therapy

RBC transfusions on RUX = 64%RUX dose adjustment for: • thrombocytopenia = 21%• anemia/hematoma = 35%

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SIMPLIFY-1

66%

Statistically significant transfusion

independence rate (p < 0.001)

vs 49% ruxolitinib

PREVENTS TRANSFUSIONS

43%PREVENTS

TRANSFUSIONS

SIMPLIFY-2

of patients were transfusion independent at week 24 on

momelotinib

Maintenance of Transfusion Independence

vs 21% best available therapy

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SIMPLIFY-1

49.1%≥ 12 WEEK TRANSFUSION

INDEPENDENCE RATE

46.6%≥ 12 WEEK TRANSFUSION

INDEPENDENCE RATE

SIMPLIFY-2

Conversion from Transfusion Dependent to Transfusion Independent

Data from Sierra’s post-hoc analyses of SIMPLIFY-1 & SIMPLIFY-2 studies

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Hemoglobin Improvement after Momelotinib Crossover

SIMPLIFY-1

9

10

11

12

13Open-Label PhaseDouble-Blind Phase

Baseline

BL 12 24 36 48 60 72 84

HG

B (g

/dL)

All patients on momelotinib

Weeks

MomelotinibRuxolitinib

Crossover

20

Non-Inferior Head-to-Head Activity on Splenomegaly

SIMPLIFY-1

SRR: Splenic Response Rate

Momelotinib statistically non-inferior to ruxolitinib on spleen (p=0.011)

Only JAKi to show equivalent splenic response to ruxolitinib in 1st-line

26.5% SRRvs 29% ruxolitinib

Pronounced Activity on Symptoms in Phase 3 Studies

TSS: Total Symptom Score*Momelotinib marginally missed Total Symptom Score (TSS) non-inferiority to RUX in SIMPLIFY-1: 28.4% vs. 42.2% (Noninferior Proportion Difference 0.00 (-0.08, 0.08)). Mean & Median Baseline TSS higher in momelotinib arm vs. RUX. No stratification for baseline symptoms in SIMPLIFY-1. 21

SIMPLIFY-1

Both momelotinib and ruxolitinib substantially improved all symptoms relative to baseline*

Med

ian

Base

line

and

Med

ian

Wee

k 24

4-W

eek

Aver

age

Sym

ptom

Sco

re

Week 24

AbDiscomfort

Itching BonePain

Night Sweats

EarlySatiety

Pain UnderLeft Ribs

Tiredness

10

9

8

7

6

5

4

3

2

1

0

MMB

RUX

absent

worst20

19

18

17

16

15

Base

line

TSS

MeanMedian

MMB arm: More symptomatic at baseline

Clinically Comparable H2H Symptom BenefitSIMPLIFY-2

26.2% TSSvs 5.9% best available therapy

Statistically Significant Symptom Response

Momelotinib compared to best available therapy (~90% ruxolitinib)

in 2nd-line patients

(p < 0.001)

Baseline

22

Noteworthy Survival Post-Ruxolitinib vs Historical Controls

Mehra et al. Blood 2016; Newberry et al, Blood 2017

Momelotinib compared to historical controls in post-ruxolitinib

treated patients

28 months vs 7-14 months*

SIMPLIFY-2

Median Overall Survival

23

Momelotinib (MMB) Ruxolitinib (RUX) Fedratinib (FED) Pacritinib (PAC)

Status in MyelofibrosisPhase 3

(Two completed P3s; P2 translational biology)

Approved(intermediate / high-risk; platelets ≥50 × 103/dL)

Post-Phase 3(P3 safety and efficacy study;

NDA Filed Q4 2018)

Phase 2(P3 trial requested by FDA;

EA MAA withdrawn)

Targets JAK1, JAK2, ACVR1 JAK1, JAK2 JAK2, FLT3 JAK2, FLT3

Splenic Response

Symptom Benefit

Anemia Benefit

Toxicity: Anemia and Thrombocytopenia LOW HIGH HIGH HIGH

Momelotinib Poised to be the Only Treatment Addressing All Three Hallmarks of Myelofibrosis

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Momelotinib 2nd-Line Market Opportunity*

*Company estimates in US and EU

• ~50K patients living with myelofibrosis

• ~75% are intermediate/high risk

Diagnosis

~70% receive 1st-line treatment1st-Line

• >70% of INT-2/Highmyelofibrosis patients have anemia

• >50% of patients aretransfusion dependent

“The majority of patients in second line would potentially be candidates for momelotinib.”

Dr. Srdan VerstovsekAnalyst Call, December 3, 2018

>75% will need 2nd-line treatment2nd-Line

Momelotinib Registration Strategy:Addressing 2nd-Line Medical Needs

• Reviewing and mining the robust body of existing clinical data generated by Gilead

• Focus on 2nd-line anemic and transfusion dependent patients, major unmet need in myelofibrosis

• Advancing regulatory interactions to determine registration path and requirements for additional Phase 3 study in 2nd-line setting

• Registration plan clarity projected for H1 2019

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Maintain maximal/stable spleen response

ANEMIACONSTITUTIONAL SYMPTOMS

SPLENOMEGALYConvert TD patients to TI

Reduce transfusionsIncrease hemoglobin

Improve constitutional symptoms

2ND-LINE DEVELOPMENT STRATEGY

SRA737 + SRA141Target ing the DNA Damage Response

SRA737: Chk1i Program Focused on Ovarian Cancer

• SRA737 has significant anti-tumor activity and profound survival benefit in CCNE1-driven background HGSOC preclinical models

• PARP inhibitors inactive in this population• Supports focus on development for ovarian cancer

27

Orthotopic PDX (CCNE1 amplified + TP53 mutated)

• Phase 2 study of Lilly’s Chk1i prexasertib in BRCA wild type (PARPi-insensitive) high-grade serous ovarian cancer demonstrates clinical efficacy in CCNE1-driven genetic background

Hong et al. Lancet Oncology 2018

Prexasertib Efficacy

33% ORR (8/24) Evaluable42% ORR (8/19) CCNE1 (All)33% ORR (4/12) CCNE1 amplification

SRA737-01 Monotherapy:Program Expansion and Prioritized Design

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• Focus on genetically-defined replication stress driven patient populations

• Continuous, daily oral administration

Dose escalation(non-selected)

Tumor SuppressorTP53, RAD50...

Oncogenic DriversCCNE1, MYC…

Replicative StressATR, CHEK1…

DNA Repair MachineryBRCA1, FANCA…

Target enrollmentN=80 (20x4)

Target enrollmentN=65

PRIORITIZING FOR OVARIAN CANCER

Prospective patient selection using NGS

technologyPhase 2 cohorts

Prostate

Non-Small Cell Lung

Head & Neck + Anus

Colorectal

Dose Optimization(non-selected)

Ovarian (CCNE1)

Ovarian (non-CCNE1)

SRA737-02 LDG Combination:Program Expansion and Amended Design

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• Low dose gemcitabine (day 1) followed by intermittent oral dosing of SRA737 (days 2 & 3); Administer weekly for 3 weeks every 28 days

Target enrollmentN=80 (20x4)

PRIORITIZING FOR OVARIAN CANCER

Dose escalation(non-selected)

Phase 2 cohorts

Continued dose escalation to MTD (non-selected)

Tumor SuppressorTP53, RAD50...

Oncogenic DriversCCNE1, MYC…

Replicative StressATR, CHEK1…

DNA Repair MachineryBRCA1, FANCA…

Prospective patient selection using NGS

technology

Ovarian

Small Cell Lung

Sarcoma

Cervical + Anogenital

SRA141:Cdc7i Program Focused on Colorectal Cancer

• SRA141: potent, orally bioavailable, selective cell division cycle 7 (Cdc7) inhibitor

• Cdc7 (serine/threonine kinase): emerging ‘next-generation’ DDR target

• Key regulator of both DNA replication and DNA damage response, as well as mitosis

30

• SRA141 IND cleared by FDA; Phase 1/2 clinical trial focused on colorectal cancer planned

• Takeda Cdc7i clinical data demonstrate preliminary monotherapy responses; P2 ongoing in colorectal

COLO205 model: TP53 & MSS - relevant genetics for Cdc7i.Tumor growth inhibition (TGI) = 99%; CRs in 4/7 (57%) animals.

t TBD Initiate Phase 1/2

31

2019 Milestones

1H 2019 Registration Plan Clarity

M O M E L O T I N I B

SRA737-01 Monotherapy 1H 2019 Preliminary Clinical Data

SRA737-02 LDG Combination 1H 2019 Preliminary Clinical Data

SRA737-03PARP Inhibitor Combination TBD Initiate Phase 1b/2

S R A 7 3 7

S R A 1 4 1

We are a clinical stage drug development company advancing targeted therapeutics for the treatment of patients with unmet medical needs in hematology and oncology

Targeted Hematology and Oncology Therapeutics

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• Bold drug development company oriented to registration and commercialization

• Lead asset, momelotinib, for the treatment of myelofibrosis with large 2nd-line market opportunity

• Two assets focused on DNA Damage Response (DDR) targeting: SRA737 and SRA141

• Highly experienced management team with proven track record in drug development

• Strong financial standing:• Shares (as of September 30):

74.4M outstanding 85.2M fully diluted

• $116.1M in cash and cash equivalents (as of September 30)

• $5M borrowed in structured debt