Q3 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

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momelotinibTARGETING JAK1/2 AND ACVR1

THERAPEUTIC FOCUS

Myelofibrosis

SRA737TARGETING Chk1

THERAPEUTIC FOCUS

Anogenital Cancer& Other Solid Tumors

SRA141TARGETING Cdc7

THERAPEUTIC FOCUS

Colorectal Cancer

DDR Network ProgramsLead Program

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

SIMPLIFY-1

SIMPLIFY-2

Myelofibrosis

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

Solid Tumors

Prostate

Myelofibrosis

Myelofibrosis

Squamous Ca.

Anogenital

Colorectal

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M O M E L O T I N I B

Prim

ary

finan

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focu

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MOMELOTINIBTarget ing JAK1, JAK2 and ACVR1

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MOMELOTINIBPositioned to potentially provide benefits on all three myelofibrosis hallmarks: symptoms, anemia and spleen

>20 studiesPhase 1, 2 and 3

>1,200 peopledosed with momelotinib

>820 patientswith myelofibrosis treated

>7 yearson treatment for several patients

Momelotinib Potentially Addresses Key Needs in Myelofibrosis Treatment

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OpportunityIntermediate/High-Risk MF who have

previously received a JAKi*; large unmet need with no approved therapies

BenefitOnly agent to robustly impact all three myelofibrosis hallmarks: constitutional

symptoms, anemia, and enlarged spleen

Robust DataTwo P3 SIMPLIFY studies

support further development; provide confidence for MOMENTUM design

RegistrationRegulatory clarity & Fast Track designation

obtained; MOMENTUM P3 study launch planned for Q4 2019; topline data anticipated Q4 2021

*Momelotinib Fast Track Designation, May 2019

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

• Ruxolitinib:• Addresses ~70% 1st-line patients• Projected global market: >$2.5B• Only treats spleen and symptoms

Anemia is not addressed by ruxolitinib

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Myelofibrosis: More Treatment Options Needed

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

• Optimal myelofibrosis therapeutic would address all three hallmarks:

• Constitutional symptoms• Anemia and transfusion dependency • Splenomegaly

Physicians need more choices than ruxolitinib

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

P R E V I O U S LY J A K i - T R E AT E D M F R E M A I N S A 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

The Three Hallmarks of a Progressive Disease

Three Hallmarks of a Progressive Disease

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> 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

Tefferi A, et al. Mayo Clin Proc. 2012

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Momelotinib: Attractive Acquisition Terms & Patent Life

• Sierra Management has unique insight into MMB.

• Full asset acquisition.

• $3M upfront; $5M at start of Phase 3.

• $195M in additional Milestones; heavily weighted to commercial success.

• Royalties from mid-teens to high-twenties; tiered by commercial success.

• Long patent life remaining: U.S. exclusivity projected to 2040* EU exclusivity projected to 2032-2040*/**

*assumes anticipated 5 years PTE and SPC extensions**pending issue

Myelofibrosis Biology: JAK1, JAK2 & ACVR1 Drive MF Disease Hallmarks

BMP2, BMP6

ACVR1

SMAD1,5P

• Aberrant activation of hepcidin transcription via hyperactivated ACVR1 signaling resulting in profound functional iron deficiency anemia

InterleukinsInterferons

Cytokine Receptors

STAT STAT

EPOR / MPL

Ligand

P

• Clonal proliferation leading to extramedullary hematopoiesis and burdensome splenomegaly

• Inflammation & aberrant cytokine signaling producing debilitating constitutional symptoms

P

JAK2/3JAK1JAK2JAK2

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Myelofibrosis Biology: Momelotinib Uniquely Inhibits All Three Disease Drivers

BMP2, BMP6

ACVR1

InterleukinsInterferons

Cytokine Receptors EPOR / MPL

Ligand

JAK2/3JAK1JAK2JAK2

• Decreased hepcidin transcription restores iron homeostasis and increases hemoglobin leading to array of anemia benefits

• Reduced extramedullary hematopoiesis improves splenomegaly

• Decreased inflammation and aberrant cytokine signaling improves constitutional symptoms

JAK1Inhibition

JAK2Inhibition

ACVR1Inhibition

SMAD1,5 PSTAT STAT PP

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Myelofibrosis Anemia:Momelotinib Could Positively Impact Multiple Pathways to Anemia

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OTHER JAKi THERAPIES

HEPCIDIN (ACVR1)

ANEMIA

Other JAK inhibitorsinduce myelosuppression

Impairment of iron metabolism

Elevated hepcidin

Activated ACVR1

EXTRAMEDULLARY HEMATOPOIESIS (JAK2)

Displacement of marrow erythropoietic tissue by fibrosis

Extramedullary hematopoiesis and splenomegaly

Inadequate extramedullary hematopoiesis and red blood cell

sequestration

INFLAMMATION (JAK1)

Pro-inflammatory cytokine profile

Impaired erythroiddifferentiation

Alterations in bone marrow cytokine

expression

Myelofibrosis Anemia: High Hepcidin & Severe Anemia Predict Poor Survival

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Pardanani et al; American Journal of Hematology 2013.

Hepcidin predicts poor survival in myelofibrosis Anemia predicts poor survival in myelofibrosis

Nicolosi M et al; Leukemia. 2018.

0 5 10Years

20 25 30 35150

2

4

6

Surv

ival

8

10

P<0.0001

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

Years

Cum

ulat

ive

Surv

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0

4

2

6

8

10

5 10 150

Myelofibrosis Anemia: 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+

Momelotinib:SIMPLIFY Data Strongly Support Benefits in Three Hallmarks of MF

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INHIBITSACVR1

INHIBITSJAK2

INHIBITSJAK1

ANEMIA

SPLENOMEGALYOnly JAKi to show equivalent splenic response to ruxolitinib in 1L

CONSTITUTIONAL SYMPTOMSPronounced TSS benefit: clinically consistent symptom improvement across all domains in 1L & 2L

Increased hemoglobin: lower rates of RBC transfusion, fewer transfusion dependent patients, etc. in 1L & 2L

Momelotinib:Regulatory Clarity Announced

• MOMENTUM Phase 3 pivotal trial designed to support registration of momelotinib

• Productive interactions with US and EU regulators

• FDA supportive of delineating a regulatory path for momelotinib in context of SIMPLIFY study data

• FDA provided constructive input to help delineate P3 study intended to yield data to support momelotinib’s potential registration

• Focus of MOMENTUM on unmet need population of 2L MF patients previously treated with a JAKi

• Momelotinib is positioned to potentially provide all three clinical benefits for this substantial population of patients: symptoms, anemia & spleen

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Momelotinib:Fast Track Designation Granted (May 2019)

Patients with intermediate/high-risk myelofibrosis who have previously received a JAK inhibitor

FDA FAST TRACK DESIGNATION

Planned Launch Q4 2019

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A Randomized, Double-Blind, Phase 3 Study to Evaluate the Activity of Momelotinib (MMB) versus Danazol (DAN) in Symptomatic, Anemic Subjects with Primary Myelofibrosis (PMF), Post-Polycythemia Vera (PV) Myelofibrosis, or Post

Essential Thrombocythemia (ET) Myelofibrosis who were Previously Treated with JAK Inhibitor Therapy

Previously Treated with JAK inhibitor

Symptomatic (TSS ≥ 10) and Anemic

(Hgb < 10 g/dL)

2:1

rand

omiz

atio

n

Double-Blind Treatment Open Label/CrossoverLong Term Follow-up

Day 1 Week 24

Primary Endpoint

Momelotinib 200 mg daily + Placebo

SubjectsN=180

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Momentum P3 Trial:Phase 3 Registration Trial Schema

Danazol has been selected as an appropriate treatment comparator given its use to ameliorate anemia in myelofibrosis patients, as recommended by NCCN and ESMO guidelines.

Spleen progression (Momelotinib 200mg)

Danazol 600 mg daily + Placebo

Momelotinib 200 mg daily

Momentum P3 Trial:Study Objectives

Primary Endpoint:• Total symptom score (TSS) response rate of MMB vs DAN at Week 24 in symptomatic and anemic

patients with PMF, post-PV myelofibrosis, or post-ET myelofibrosis who were previously treated with an approved JAK inhibitor therapy.

Secondary & Exploratory Endpoints:• Transfusion independence (TI) rate at Week 24 for subjects treated with MMB vs DAN.• Splenic response rate (SRR) at Week 24 for subjects treated with MMB vs DAN.• Duration of TSS response for subjects treated with MMB.• Other measures of anemia benefit, including TD-TI rate and measures of cumulative transfusion burden.• Additional Patient Reported Outcomes, including assessments of fatigue and physical function.

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Momentum P3 Trial:Key Design Elements

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Endpoint Order & Powering Supporting Data/Rationale

Symptom (TSS) response rate Primary (W24)99% powered; p<0.05

FDA preferred measure of clinical benefit in MyelofibrosisConsistent and meaningful TSS responses in S-1 & S-2

Transfusion Independence rate Secondary (W24)>90% powered; p<0.05

Favorable & statistically significant TI rates in S-1 & S-2

Spleen (SRR) response rate Secondary (W24)>90% powered; p<0.05

Defined washout allows for splenic rebound & SRR benefitNon-inferior SRR benefit H2H vs RUX in S-1

Durability of TSS response Secondary (W48) Durability of symptomatic benefit to W48 established in S-1 & S-2

Other anemia measures Secondary & Exploratory Consistent suite of benefits: TD-TI rates, improved HGB, reduced transfusion frequency, etc.

Chief Investigator:Dr. Srdan Verstovsek, MD Anderson Cancer Center, Houston, Texas, USA

*Stratified for baseline TSS, RBC transfusions & spleen

**Dependent on regulatory review process (priority or standard)

Momentum P3 Trial:Key Trial Assumptions

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Key Assumption Comment*

# Patients 180 (2:1 randomization)

Territory Global study: North America, EU, APAC, etc.

Study Start Planned launch in Q4 2019

Estimated Time to Enroll ~18 months

Estimated Time to Primary Endpoint ~6 months to primary endpoint after enrollment

Estimated Topline Data ~Q4 2021

Estimated Filing Date ~Q2 2022

Potential Regulatory Approval ~Q4 2022-Q2 2023**

*Company estimates

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Momentum P3 Trial:Chief Investigator

• Dr. Srdan (Serge) Verstovsek, Chief, Section for Myeloproliferative Neoplasms, MD Anderson Cancer Center, Houston, has been named Chief Investigator of MOMENTUM.

• World-renowned physician-scientist, and a leading global authority on the treatment of myelofibrosis.

• Dr. Verstovsek’s clinical and translational research is focused on understanding the biology of and developing new therapies for myeloproliferative neoplasms (MPNs).

• Principal investigator for more than 50 clinical trials testing novel therapies for patients with MPNs.

• Published more than 400 peer-reviewed manuscripts. • Recipient of numerous awards and accolades. Srdan Verstovsek, MD, PhD

Chief, Section for Myeloproliferative Neoplasms, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston.

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Momentum P3 Trial:KOL Views on Danazol Use in MF

References citing danazol in MF: • Cervantes F, Isola IM, Alvarez-Larrán A, et al. Danazol therapy for the anemia of myelofibrosis: assessment of efficacy with current criteria of response and long term results. Annals

of Hematology. 2015; 94(11):1791-6.• Cervantes F, Alvarez-Larrán A, Domingo A, et al. Efficacy and tolerability of danazol as a treatment for the anaemia of myelofibrosis with myeloid metaplasia: Long term results in 30

patients. British Journal of Haematology. 2005; 129: 771–5.• Cervantes F, Hernández-Boluda JC, Alvarez A, et al. Danazol treatment of idiopathic myelofibrosis with severe anemia. Haematologica 2000; 85:595-9.• Luo X, Xu Z, Li B, et al. Thalidomide plus prednisone with or without danazol therapy in myelofibrosis: a retrospective analysis of incidence and durability of anemia response. Blood

Cancer Journal. 2018; 8:9. • Gowin K, Kosiorek H, Dueck A, et al. Multicenter phase 2 study of combination therapy with ruxolitinib and danazol in patients with myelofibrosis. Leukemia Research 2017;60:31-5.• Levy V, Bourgarit A, Delmer A, et al. Treatment of agnogenic myeloid metaplasia with danazol: A Report of Four Cases. American Journal of Hematology. 1996;53:239-41. • Chabannon C, Pegourie B, Sotto JJ, et al. Clinical and hematological improvement in a patient receiving danazol therapy for myelofibrosis with myeloid metaplasia. Nouv Rev Fr

Hematol. 1990;32(2):165-6.• Xu ZF, Qin TJ, Zhang HL, et al. Ruxolitinib combined with prednisone, thalidomide and danazol for treatment of myelofibrosis: a pilot study.

“In my experience as a practicing hematologist who has treated many patients with danazol, I do not believe danazol will have any marked activity on symptoms and spleen, and small benefit on anemia in these late stage patients; as such, the use of danazol as a control arm in MOMENTUM is appropriate as we expect it to have minimal activity and enable us to see a very strong treatment effect.”

Dr. Serge Verstovsek June 10, 2019Srdan Verstovsek, MD, PhDChief, Section for Myeloproliferative Neoplasms, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston.

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EXTENDED ACCESS PROGRAM

Momelotinib:Totality of Data to Support Potential Registration

PHASE 3 CLINICAL TRIAL

Patient data from completed studies>600 subjects

• Statistically non-inferior spleen response vs. RUX (S-1; p = 0.011)

• Statistically significant TSS response vs. BAT/RUX (S-2; p < 0.001)

• Statistically significant transfusion independent rates (S-1; p < 0.001) (S-2; p = 0.001)

• Crossover data: momelotinib efficacy and safety data in patients who switch from RUX (S-1) or BAT/RUX (S-2) after Week 24

SIMPLIFY-1SIMPLIFY-2

‘1672

XAPTRANSLATIONAL BIOLOGY STUDY IN TD PATIENTS

Pivotal study data~180 subjects

• Primary endpoint: TSS response rate (99% powered; p<0.05)

• Secondary endpoints:• Transfusion Independence rate• Spleen (SRR) response rate• Durability of TSS response• Other anemia measures

Long term treatment data>130 subjects; >15 countries

• Durable response data (some patients treated>8 years)

• Long term safety and tolerability data

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Momelotinib 2nd-Line Market Opportunity*

• ~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 VerstovsekJune 2019

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

Favorable patent exclusivity • potential extensions to 2040** provide a

compelling commercial opportunity

*Company estimates**assumes anticipated 5 years PTE and SPC extensions

Planned Launch Q4 2019

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FDA FAST TRACK DESIGNATION

SRA737

Target ing Chk1

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SRA737 Program Overview:Broad Signal Seeking Across Indications & Genetics

SRA737 Monotherapy (-01)

SRA737 + LDG (-02)

Intrinsic RS

Intrinsic +Extrinsic RS

Tumor SuppressorTP53, RAD50...Oncogenic DriversCCNE1, MYC…

Replicative StressATR, CHEK1…

DNA Repair MachineryBRCA1, FANCA…

mCRPC

NSCLC

SCC (H&N, anogenital)

HGSOC

mCRC Indication/genomic signature with

enriched response to SRA737 +/-LDG

SCLC

Cervical/Anogenital

HGSOC

STS

Clinical Trial Clinical Hypothesis Indications Tumor Genetics Ph2 Directional Efficacy Signal

SRA737 is an active and well tolerated drug candidate that warrants further development. Sierra is evaluating potential next steps for SRA737, exploring options that could enable its continued advancement, while focusing the company’s resources on momelotinib.

SRA737+LDG:Demonstrates Anti-Cancer Activity Across Multiple Indications

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• PRs observed in six subjects (3x anogenital cancer; 1x rectal, cervical, and ovarian cancer). Generally, responses were first recorded at the end of Cycle 2 (first on-study scan).

• 41 subjects had best response of Stable Disease (SD); durable SD lasting ≥ 4 months was recorded in 32 subjects and was observed in all expansion cohorts.

SRA737+LDG:Promising 30% Response Rate in Anogenital Cancer

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Noteworthy anti-tumor activity observed in subjects with advanced anogenital cancer (ORR = 30%; DCR=60%)

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SRA737+LDG in Anogenital Cancer:Illustrative Clinical Activity

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70 yo male with anal cancer; extensive liver metastasisPrior therapy: radiation and 1 line of systemic therapy Genetic Profile: FA/BRCA, PI3K and TMB-IBest tumor response: -41% Duration on treatment: 11 cycles (response ongoing at discontinuation; patient decision)

59 yo female with anal cancer, mediastinal mass compression and malignant pleural effusionPrior therapy: 3 lines of systemic therapy FMI Genetics: FA/BRCA and TMB-IBest tumor response: -26% + resolution of pleural effusionDuration on treatment: 7 cycles; ongoing (as of data cut: 03 May 2019)

Targeted Hematology and Oncology Therapeutics

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• Bold drug development company oriented to potential registration and commercialization

• Momelotinib – differentiated JAKi potentially addressing all three hallmarks of myelofibrosis• MOMENTUM P3 in 2L MF planned launch in Q4 2019

• SRA737 oriented to potential registration-intent studies in anogenital cancer; exploring non-dilutive options to advance

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

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

74.7M outstanding 88.0M fully diluted

• $78.8M in cash and cash equivalents (as of June 30)

• $5M borrowed in structured debt

NASDAQ: SRRA