Beyond PARP - Next Generation DDR TherapeuticsQ1 2017

SIERRA ONCOLOGY

Safe Harbor Statement

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Except 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 to differsignificantly from those expressed in any forward-looking statement. In some cases, you can identify forward-lookingstatements by terminology such as “may”, “will”, “should”, “plan”, “predict”, “expect,” “estimate,” “anticipate,” “intend,”“goal,” “strategy,” “believe,” and similar expressions and variations thereof. Forward-looking statements may includestatements regarding the Company’s business strategy, potential growth opportunities, clinical development activities,the timing and results of preclinical research, clinical trials and potential regulatory approval and commercialization ofproduct candidates. Although the Company believes that the expectations reflected in such forward-looking statementsare reasonable, the Company cannot guarantee future events, results, actions, levels of activity, performance orachievements. These forward-looking statements are subject to a number of risks, uncertainties and assumptions,including those described under the heading “Risk Factors” in documents the Company has filed with the SEC. Theseforward-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. TheCompany believes such information is accurate and that the sources from which it has been obtained are reliable.However, the Company cannot guarantee the accuracy of, and has not independently verified, such information.

Trademarks:

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SIERRA ONCOLOGY

Sierra Oncology

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A clinical-stage drug development company advancing next generation DNA Damage Response (DDR) therapeutics for the treatment of patients with cancer.

NASDAQ: SRRA

Headquarters: Vancouver, BCDevelopment: San Francisco, CA

Pro forma Shares (12/31/16): 52.7M* outstanding59.3M* fully diluted

Pro forma Cash on hand (12/31/16):$136.3M*

*includes February 2017 financing (~$27.3M; 21.8M shares) net of underwriting discounts, commissions and offering expenses.

• We are an ambitious oncology drug development company oriented to registration and commercialization.

• We have a world-class management team with a proven track record in oncology drug development.

• Our two product candidates, SRA737 and SRA141, target the DNA Damage Response (DDR) network, a scientifically validated approach on the leading edge of cancer biology with broad potential across oncology.

• Our DDR program expands beyond PARP inhibitors, to provide for broader clinical and commercial opportunity.

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Our Pipeline of ‘Next Generation’ DDR Therapeutics

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Preclinical Phase 1 Phase 2

Targeting Cell division cycle 7 (Cdc7)

Phase 1 MonotherapyAdult solid tumors, Currently enrolling

Phase 1 CombinationAdult solid tumors, Currently enrolling

Plan to file IND H2 2017

Targeting Checkpoint kinase 1 (Chk1)SRA737

SRA141

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Our Next Generation DDR Portfolio: SRA737 & SRA141

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• Highly-selective small molecule inhibitor of the serine-threonine kinase Checkpoint kinase 1 (Chk1).

• Chk1 is a central regulator of the DDR network and of multiple cell cycle checkpoints.

• Oral bioavailability of SRA737 affords greater flexibility in dosing strategies compared to IV agents.

• Currently in two Phase 1 clinical trials in patients with advanced cancer.

• Highly-selective small molecule inhibitor of the serine-threonine kinase Cell division cycle 7 (Cdc7).

• Cdc7 is a key regulator of DNA replication and the DDR network.

• Broad development scope in solid and liquid tumors.

• Mono- and combo- therapy development potential.

• Clinical studies expected to begin by the end of 2017.

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Beyond PARP: Our DNA Damage Response (DDR) Program

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Our DNA is Under Constant Attack

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• Our DNA is continuously subject to damage through a variety of endogenous and exogenous mechanisms.

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The DDR Network Detects & Repairs Damaged DNA

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• The DDR network is a system of cellular pathways that monitor and repair DNA damage to maintain genomic integrity throughout the cell cycle.

• The DDR network comprises cell cycle checkpoints, which temporarily inhibit cellular replication to repair damaged DNA.

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Sierra Oncology’s DDR Program: Expanding Beyond PARP

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• PARP inhibitors are intended to prevent the repair of DNA single strand breaks.

• Our DDR program expands beyond the scope of PARP inhibitors.

• We focus on impeding the repair of DNA double strand breaks, the most deleterious form of DNA damage, as well as by striking at targets that control DNA replication and cell cycle progression.

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Burgeoning Scientific Validation for Targeting DDR

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Focus Issue: DNA Damage RepairJune 2016June 2016

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Industry Validation of DDR’s Potential in Cancer: PARP Inhibitors Lead The Way

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May 2016

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Clinical Proof of Concept for Drugging the DDR: Key Data Summary

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PARP inhibitor: olaparib

• 14/16 (88%) response rate in metastatic prostate in a retrospective analysis of biomarker positive patients with DDR mutations.

Wee1 inhibitor: AZD1775

• 2 PRs in SCLC; both patients had mutations in TP53 and RB1, one also had BRCA1 mutation.

• 2 PRs in monotherapy: 1 PR head-and-neck had BRCA mutation, 1 PR in ovarian had BRCA mutation.

• 27% PR rate in combo with carboplatin in TP53 mutated ovarian cancer refractory/resistant to carboplatin + paclitaxel.

ATR inhibitor:VX-970

• 4 PRs (17%), 12 SDs (52%) in combination with cisplatin in platinum resistant or refractory ovarian cancer with no patient selection/enrichment.

Chk1/2 inhibitor: LY2606368

• 5/13 PRs (38%) response rate in high grade serous ovarian cancer, non-BRCA mutated.

Chk1/2 inhibitor: AZD7762

• Durable 3+ year CR in combinations with irinotecan in invasive small cell cancer of the ureter having RAD50 and TP53 mutations.

Chk1 inhibitor: GDC-0575

• 1 CR (ongoing >9 months) in sarcoma with lung metastases; 1 PR (lasted >1 year) in TP53 mutated leiomyosarcoma with extensive metastases; both in combination with low dose gemcitabine.

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SRA737 Targeting Chk1

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SRA737: Exemplary Pedigree

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CRUK/ICR drug discovery track record:Discovered and advanced into the clinic by:

Temozolomide for glioblastoma

>$1B ww sales*

Abiraterone (Zytiga) for advanced

prostate cancer>$2B ww sales*

*2016

*2008

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SRA737: Potential Best-In-Class Characteristics

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Criterion SRA737 LY2606368

Presentation: Oral i.v.

Biochemical IC50: Chk1 1.4 nM ~1 nM

Biochemical IC50: Chk2 1850 nM 8 nM

Selectivity: Chk1 vs. Chk2 1320x ~10x

10 mg/kg in BALB/c mice

• SRA737 is orally bioavailable, potent, and highly selective for Chk1 over Chk2.

• SRA737 has an excellent PK profile, and demonstrates robust efficacy in numerous in vivo cancer models as a single agent and in combination.

HT29 CRC

• SRA737 selectivity: 15/124 kinases at 10 µMERK8 = 100x All other kinases >200xCDK2 = 2750xCDK1 = 6750x

Cmin

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Two Key Roles for Chk1:An Important DDR Component

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• DNA damage can be resolved by several complementary mechanisms that are activated by DNA damage sensing factors.

• Homologous recombination repair (HRR) is an error-free repair process employed in response to double strand breaks and collapsed replication forks.

• One of Chk1’s functions is as a critical component of the HRR machinery.

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Two Key Roles for Chk1:A Critical Cell Cycle Checkpoint

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• Replication stress induced by oncogenic drivers (e.g. MYC and RAS) combined with loss of function in tumor suppressors (e.g. TP53 and ATM) results in persistent DNA damage and genomic instability.

• Cancer cells tolerate genomic instability and elevated DNA damage due to an over-reliance on Chk1, a key S Phase and G2/M checkpoint.

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SRA737 Targeting Chk1:Striking at an Achilles’ Heel of Cancer

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• Synthetic lethality may be achieved in these genetically mutated cancer cells by inhibiting Chk1, a critical remaining component of the DDR network that is now essential to replication.

• With Chk1 inhibited by SRA737, tumor cells are expected to proceed through the S Phase and G2/M checkpoints, leading to mitotic catastrophe resulting in cell death.

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Biology of SRA737 Sensitivity:Exploiting Cancer’s Genetic Alterations

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• Synthetic lethality due to Chk1 inhibition has been linked to four major classes of genetic alterations:

• Tumor suppressors (e.g. TP53, RAD50, etc.)

• Oncogenic drivers (e.g. MYC, KRAS, etc.)

• Replicative stress(e.g. ATR, CHEK1, etc.)

• DNA repair mutations (e.g. BRCA1, BRCA2, FA, etc.)

• Exogenous drivers of DNA damage, like chemotherapy, are also demonstrated to enhance SRA737 sensitivity.

• Our clinical approach is to select patients with defined genetic alterations to create synthetic lethal backgrounds for SRA737 therapy.

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Optimizing Sensitivity to SRA737 in the Clinic

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• Most studies with DDR agents focus on one enhancer of sensitivity, e.g. defects in DDR or TP53 mutation, if at all.

• Sierra Oncology’s hypothesis is that optimal sensitivity is achieved by combining defects:

Combining multiple mechanisms known to enhance Chk1 sensitivity could “stack the deck” in favor of clinical activity with SRA737.

(G1/S guardians)

(BRCA1/BRCA2/FA)

Oncogenic Driver

(MYC, KRAS)

(ATR/CHEK1)

(G1/S guardians)

(G1/S guardians)

Exogenous Drivers

+/-

+

+

+

Chk1: S & G2/M checkpoint reliance

Chk1: DDR & replication stress

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SRA737: Significant Therapeutic Potential Across Oncology

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ChemotherapyCombinations with DNA damaging chemotherapy

DDR CombinationsSynergy with other

DDR targeting agents to maximize DNA

damage

RadiotherapySensitize to ionizing radiation

Immuno-OncologyDDR targeting agents coupled

with immune activation

DDR MonotherapyExploit replicative stress and genetic

instability for synthetic lethality

SRA737

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SRA737: Overall Development Strategy

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I/O Combo

ChemotherapyGemcitabine and gemcitabine/cisplatin combinations exploit profound potentiatingeffects of SRA737.

Chk1 inhibitor + PARP inhibitor might expand/enhance PARP inhibitor sensitivity.

PD-(L)1 combination marries potential driver of neoantigen presentation in “double checkpoint” strategy.

MonotherapyExploit synthetic lethality in genetically-defined populations with predicted high sensitivity to SRA737.

PARP Combo

Potential Clinical Opportunities

Current Clinical Trials

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Two Clinical Trials Initiated at Royal Marsden, UK -Current Study Designs

A Phase I Trial of CCT245737 (SRA737) in Patients with Advanced CancerClinicalTrials.gov Identifier: NCT02797964

Estimated Enrollment: • 40 patients with advanced solid tumors

A Phase I Trial of CCT245737 (SRA737) in Combination with Gemcitabine Plus Cisplatin or Gemcitabine Alone in Patients with Advanced CancerClinicalTrials.gov Identifier: NCT02797977

Estimated enrollment: • 70 patients with advanced solid tumors

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• Sierra Oncology assumed ownership of the ongoing SRA737 clinical trials in Jan 2017.• Formal sponsor transition has now occurred, enabling modifications to the trial designs.• We have submitted protocol amendments intended to enhance both of these studies,

including to pre-select patients predicted to most likely derive benefit from SRA737 treatment.

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Genomic Alterations Differ Across Indications: ‘Right Genetics In The Right Patients’

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• Mutational frequencies (oncogenic drivers; replications stress; DNA repair; tumor suppressors) differ across indications.

• Certain cancer indications harbor significant genomic instability, and we believe are promising target indications for therapeutic intervention with SRA737.

• Sierra Oncology’s clinical development strategy: genetically-defined patient selection in indications predicted to be sensitive to SRA737 inhibition.

Red = most frequently mutated; Green = least frequently mutated

Bladder11 6 6 11

Ovarian 6 10 10 5

Squamous NSCLC8 5 11 7

Prostate5 7 8 10

Colorectal9 9 1 8

Head & Neck10 2 9 4

Lung Adenocarcinoma4 8 7 6

Pancreatic7 11 1 2

Cholangiocarcinoma2 3 1 9

Invasive Breast3 4 5 3

AML1 1 1 1

+

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Proposed Protocol Amendments –Genetic Selection Strategy in Defined Cancers

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Enroll subjects with a minimum of two types of genetic abnormalities including:

All patients:• a deleterious mutation in a key tumor

suppressor gene, such as TP53.

Plus at least one of the following:• a loss of function or deleterious mutation in the

DNA damage response pathway such as ATM, BRCA1, BRCA2.

• a genetic indicator of replicative stress, defined as gain of function or amplification of CHK1 or ATR or other related gene.

• a gain of function mutation or amplification of an oncogenic driver such as MYC, RAS.

Evaluate cancer indications predicted to have a high prevalence of Chk1-sensitizing genetic aberrations such as:

Monotherapy:• previously treated metastatic colorectal cancer• platinum-resistant ovarian cancer• metastatic castration-resistant prostate cancer• advanced non-small cell lung cancer• head and neck squamous cell carcinoma

Combination:• bladder cancer • pancreatic cancer

Sierra intends to amend the ongoing clinical trials to include the following patient enrichment strategies:

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SRA737: Upcoming Milestones

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Medical conference data

2018

Complete formal CTA transfer

Q1 2017

Preliminary ‘Synthetic Lethality’ update

~Y/E 2017

Medical conference data

2018

Complete formal CTA transfer

Q1 2017

Preliminary ‘Combination’ update

~Y/E 2017

Chk1i + PARPi preclinical dataH2 2017

Chk1i + PD(L)-1 preclinical dataH2 2017

Q1 17 Q2 17 Q3 17 Q4 17 Q1 18 Q2 18

Monotherapy

Chemo Combo

PARP Combo

I/O Combo

Potential Clinical Opportunities

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SRA141 Targeting Cdc7

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SRA141: Selective Small Molecule Targeting Cdc7

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• SRA141: highly-selective and potent cell division cycle 7 (Cdc7) inhibitor.

• Cdc7: key regulator of both DNA replication and DNA damage response.

• Broad development scope in solid and liquid tumors.

• Mono- and combo- therapy development potential.

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Cdc7: Key Function in the DDR Network

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• Cdc7 activates DNA replication during S-phase in response to growth promoting signals (e.g. cyclins, Myc, Ras) and stabilizes stalled replication forks during replication stress.

• Stalled replication forks activate ATR and Chk1 signaling.

• Potential synergies may be achieved by combining Cdc7, such as with Chk1 inhibition.

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SRA141: Potential First-In-Class/Best-In-Class Opportunity

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• Preclinical data and published literature suggest a variety of indications with potential for response to Cdc7 inhibitors:

• Solid tumors: breast, ovarian, pancreatic, melanoma, colorectal, uterine, thyroid, etc.

• Hematological malignancies: AML, DLBCL, etc.

• SRA141’s selectivity profile offers possible differentiation and potential safety and efficacy advantages.

• A biomarker-driven patient selection strategy focusing on drivers of Cdc7 inhibitor sensitivity may help facilitate clinical trial execution.

• Clinical studies expected to begin by the end of 2017.

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Advancing Targeted Cancer Therapies

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Proven Leadership in Oncology Development

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Nick Glover, PhDPresident and CEO

Barbara Klencke, MDChief Development Officer

Angie You, PhDChief Business & Strategy Officer and Head of Commercial

Sukhi Jagpal, CA, CBV, MBAChief Financial Officer

Mark Kowalski, MD, PhDChief Medical Officer

Keith Anderson, PhDSenior Vice President, Technical Operations

Wendy ChapmanSenior Vice President, Clinical Operations

Diane GardinerSenior Vice President, Human Resources and Administration

Christian Hassig, PhDSenior Vice President, Research

Chandra LovejoySenior Vice President, Global Regulatory Affairs and Head of Quality

Emma McCannSenior Vice President, Program Management

Gregg Smith, PhD, MBASenior Vice President, Preclinical

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Our DDR Program Expands Beyond PARP

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We have established a promising portfolio of DDR assets:• SRA737 and SRA141 target the DNA Damage Response network, a promising

approach to treating cancer based on leading-edge discoveries in cancer biology.

• Our DDR program expands beyond the scope of PARP inhibitors by focusing on DNA double strand breaks, replication, genomic instability and cell cycle checkpoints.

• The near-term development plan for SRA737, our Chk1 inhibitor, encompasses synthetic lethality as monotherapy, and in combination with DNA-damaging chemotherapy.

• Two Phase 1 clinical trials with SRA737 are underway; a preliminary update is anticipated ~Y/E 2017.

• Preclinical research is underway combining SRA737 with other DDR agents (e.g. PARPi), and in combinations with immuno-oncology.

• SRA141, our Cdc7 inhibitor, is in preclinical development with clinical studies expected to begin by the end of 2017.