The Final Phase: Bringing Momelotinib to Patients A Data Update and KOL Discussion June 21, 2021 1 SAFE HARBOR STATEMENT Except for statements of historical fact, any information contained in this presentation may be a forward-looking statement 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 differ significantly from those expressed in any forward-looking statement. In some cases, you can identify forward- looking statements by terminology such as “may”, “will”, “should”, “plan”, “predict”, “expect,” “estimate,” “anticipate,” “intend,” “goal,” “strategy,” “believe,” and similar expressions and variations thereof. 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Such use should not be construed as an endorsement of such products. 2 Today’s Agenda Welcome & Introduction Stephen Dilly, MBBS, PhD President & Chief Executive Officer Momelotinib’s Impact on the Burdens of Myelofibrosis Barbara Klencke, MD Chief Medical Officer Stephen Oh, MD, PhD Importance of Treating Anemia in Myelofibrosis Siteman Cancer Center Washington University School of Medicine Association Between Transfusion Independence and Overall Survival; Aaron Gerds, MD Taussig Cancer Institute Impact on Transfusion Independence by Baseline Status Cleveland Clinic Aaron Gerds, MD Panel Discussion Taussig Cancer Institute Cleveland Clinic samantha Stephen Oh, MD, PhD Siteman Cancer Center Washington University School of Medicine Srdan Verstovsek, MD, PhD University of Texas MD Anderson Cancer Center Open Q&A 3 Momelotinib Progress Update Stephen Dilly, MBBS, PhD President & Chief Executive Officer 4 MOMENTUM Enrollment Complete! 195 Patients Enrolled vs. 180 Planned 5 Momelotinib Progresses as Sierra’s Flagship Compound MOMENTUM Progress Myelofibrosis Near-term Focus with • Trial has completed Opportunity Long-term Planning enrollment with 195 • MMB profile offers • Preparing for NDA patients unique value proposition filing and potential US • Topline data for underserved MF launch anticipated Q1 2022 patients • Identifying early-stage • Completes data set • Potential for MMB programs with for FDA filing combination studies significant promise On a Quest to Deliver Targeted Therapies for Rare Cancers 6 Pivotal Phase 3 ‘MOMENTUM’ Study: Enrollment Complete and Awaiting Topline Results Long Term Double-Blind Treatment Open Label/Crossover Follow-up Subjects Momelotinib 200 mg daily Previously Treated N=180 + Placebo with JAK inhibitor Early crossover to open label in the event of Symptomatic (TSS ≥ 10) confirmed symptomatic splenic progression Momelotinib and Anemic 2:1 randomization 200 mg daily (Hgb < 10 g/dL) JAKi taper/washout Danazol* 600 mg daily ≥ 21 day + Placebo Primary Endpoint Day 1 Week 24 Primary Endpoint Secondary Endpoints • Total symptom score (TSS) response rate • Transfusion independence (TI) rate at Week 24 at Week 24 • Splenic response rate (SRR) at Week 24 *Danazol was selected as an appropriate comparator given its use to ameliorate anemia in MF patients, as recommended by NCCN, ESMO guidelines. 7 Momelotinib’s Impact on the Burdens of Myelofibrosis Barbara Klencke, MD Chief Medical Officer 8 Significant Need Remains in Myelofibrosis Treatment Improved Survival Anemia is a major problem. …It’s present at…[diagnosis]… in about a third of patients. …after 1 year, two-thirds are already • Generally incurable (for most) anemic. I don’t have a good medication to give them. Patients may • Median survival is 2-8 years after diagnosis have exacerbation of anemia while on JAK inhibitors. Anemia is driven by degree of anemia, other factors(1) a target for new medication to develop – Srdan Verstovsek, MD, PhD (2) • Durability of activity • Current treatments are often dose limited by platelet counts, anemia Our goals for the future are to expand the breadth of response, • Favorable hematologic safety profile could beyond spleen and symptoms, … to include progression-free enable long term higher dose intensity and and overall survival…and to improve anemias or cytopenias durable disease control – Ruben Mesa, MD (2) Therapy for Cytopenic Patients • Anemia One area that needs significant attention is patients who have myelofibrosis and thrombocytopenia. …in addition to having • Common and progressive worse overall survival, these patients do not have good • Current treatments worsen anemia treatment options – Pankit Vacchini, MD (2) • Thrombocytopenia • Can be a manifestation of disease • Current treatments decrease platelet levels (1) Cervantes F, et al.. Blood. 2009;113(13):2895-2901 (2) Source: Edited transcript from Ongoing Unmet Needs and New Approaches in Myelofibrosis, OncLive, April 14, 2021. 9 Current Treatment Paradigm Comes at a Cost Current Treatment Goal: Comes at a Cost: Managing Spleen and/or Symptoms Worsening Anemia and/or Thrombocytopenia Enlarged Spleen Symptoms Anemia / Transfusions Low Platelet Count 50 – 70% 40 – 60% 70 – 90% 10 – 30% of patients at diagnosis of patients at diagnosis of patients at diagnosis of patients at diagnosis Additional Factors Should be Considered in Future Treatment Paradigm Source: Internal data on file. 10 All Four Factors Play a Role in Treatment Decisions Optimal Treatment Goal: Durably Manage Spleen, Symptoms & Anemia / Transfusion Requirements while Maintaining Platelet Count and Dose Intensity Enlarged Spleen Symptoms Anemia / Transfusions Low Platelet Count 50 – 70% 40 – 60% 70 – 90% 10 – 30% of patients at diagnosis of patients at diagnosis of patients at diagnosis of patients at diagnosis Hemoglobin Level and Platelet Count Must be Considered When Choosing Future Treatment 11 Source: Internal data on file. Mechanism of Action: Momelotinib Inhibits JAK1, JAK2 and ACVR1/ALK2 Interleukins Interferons Ligand BMP2, BMP6 Cytokine Receptors EPOR / MPL ACVR1 / ALK2 JAK2 JAK2 JAK2 JAK1 JAK2 MOMELOTINIB MOMELOTINIBInhibition MOMELOTINIB JAK1 JAK2 STAT JAK1 JAK2 STAT JAK1 JAK2 P P SMAD1,5 ACVR1 ACVR1 ACVR1 P Hyperactive JAK-STAT signaling results in Preclinical and clinical studies suggest that the clinical overproduction of multiple inflammatory cytokines anemia benefits of momelotinib result from suppression in MF, which act both locally and systemically of ACVR1/ALK2-mediated hepcidin production Momelotinib Inhibits all Three Disease Drivers, Potentially Improving Splenomegaly and Symptoms of Myelofibrosis While Maintaining or Improving Hemoglobin Asshoff, M. et. al. Blood. 2017;129(13):1823-1830. 12 Oh, S. et al. Blood Advances. 2020;4(18):4282-4291. Momelotinib’s Unique MOA May Lead to Durable Responses for Symptomatic & Anemic MF Patients MMB has the Potential to MMB is a Differentiated JAK Provide Significant and Durable Inhibitor Enabling Benefits for Patients with MF Clear Patient Segmentation • Reduced transfusion burden and improved • Clinically meaningful anemia benefits, symptom transfusion independence for anemic patients and spleen control, without impacting platelets and those at risk of developing anemia • Low potential for myelosuppression supports • Achieving TI could become the primary driver of dosing intensity & durable activity treatment decisions in MF • Some patients remain on full dose of MMB for >10 • MMB retains robust activity irrespective of years baseline platelet count • Robust and meaningful survival duration achieved • Optimal treatment for patients with MF who in both the JAKi-naïve and JAKi-exposed patients are, or are at risk of becoming, anemic and/or thrombocytopenic 13 Completed Phase 3 Studies SIMPLIFY-1 and 2 SIMPLIFY-1 SIMPLIFY-2 1st-Line Population 2nd-Line Population JAK inhibitor naïve Prior ruxolitinib complicated by hematologic toxicity Primary Endpoint Primary Endpoint Day 1 Week 24 Year 7 Day 1 Week 24 Year 7 Randomized treatment Extension LTFU Double-blind treatment Open label LTFU Momelotinib Momelotinib RUX-exposed 200 mg QD JAKi-naïve 200 mg QD Open label, Momelotinib Momelotinib 200 mg QD Double-blind, N=156 Best available Ruxolitinib 200 mg QD N=432 therapy 20 mg BID 2:1 randomization 1:1 randomization