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Transformational Science Advancing Oncology
Disclaimer This presentation contains forward-looking statements about BeyondSpring Inc. ("BeyondSpring" or the "Company"). Forward looking statements are based on our management's beliefs and assumptions and on information currently available to our This presentation contains forward-looking statements about BeyondSpring Inc. ("BeyondSpring" or the "Company"). Forward looking statements are based on our management's beliefs and assumptions and on information currently available to our management, including those described in the forward-looking statements and risk factors sections of the Company's 20-F and other filings with the SEC, which are available on BeyondSpring's Investor Relations website.Such statements are subject to known and unknown risks, uncertainties, and other factors that may cause our or our industry's actual results, levels of activity, performance, or achievements to be materially different from those anticipated by such statements. In some cases, you can identify forward-looking statements by terminology such as "may," "will," "should," "expects," "plans," "anticipates," "believes," "estimates," "predicts," "potential," "intends," or "continue," or the negative of these terms or other comparable terminology. Forward-looking statements contained in this presentation include, but are not limited to, (i) statements regarding the timing of anticipated clinical trials for our product candidates and our research and development programs; (ii) the timing of receipt of clinical data for our product candidates; (iii) our expectations regarding the potential safety, efficacy, or clinical utility of our product candidates; (iv) the size of patient populations targeted by our product candidates and market adoption of our product candidates by physicians and patients; and (v) the timing or likelihood of regulatory filings and approvals. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future.
* Corporate Overview Lead drug candidate Plinabulin with two indications in pivotal studyPrevention of Neutropenia caused by chemotherapy regimensNon Small Cell Lung Cancer (NSCLC) in patients with measurable lesionsDual-track development in US and China, supported by one global study Follow-on indications for Plinabulin (PD-1 combination, RAS mutations, brain tumors, etc) Wholly owned portfolio of novel immuno-oncology assets Scalable Business Model Well Positioned to Execute on Strategic Plan Seasoned management team supported by KOLs and medical advisory boardCash of $54.6M* - funds pipeline development, including through submission of 2 NDA's Focus on approvals in U.S. and China, with unique access to large marketsPotential for accelerated clinical developmentEarly-stage pipeline includes next-generation immuno-oncology assets and new products from Fred Hutchinson/UW collaboration * As of March 31, 2017
* Plinabulin Preclinical Phase 1 Phase 2 Phase 3 Status Plinabulin Prevention of Neutropenia(in chemo induced Neutropenia) Study 105 (docetaxel) IND Initiation 2Q 2017First Data Readout: 2H 2017 Study 106 (TAC) First Data Readout: 1H 2018 NSCLC: Measurable lung tumor (+ Docetaxel) Initiation 2Q 2016 Readout: 1Q 2018 (interim) PD-L1+(+ Nivolumab) Initiation 2H 2016Readout: 2017 KRAS Mutant(+ Docetaxel) Initiation 2017 Metastatic Brain Tumor (+ Radiation) Initiation 2017 IO Compound BPI-002 (T-cell activation) Preclinical IO Compound BPI-003 (IKK inhibitor) Preclinical IO Compound BPI-004 (Neo-Antigen) Preclinical Fred Hutchinson/UW Collaboration (Ubiquitination technology platform) Preclinical Pipeline Overview
* Plinabulin Dendritic Cell Neutropenia Prevention Effects Plinabulin: Novel Structure and Novel IO Target (GEF-H1) JNK Activation Rho Activation Immune - Related Anticancer Effects Plinabulin Kashyap A et al. Keystone Meeting Mar. 2017Wang Y et al. FEBS J. 2016; 283: 102-111 300 derivatives
* Chemotherapy-Induced Neutropenia Causes: Neutropenia Treatment With G-CSF Causes: Bacterial related mortalitiesDelays in chemo dosingChemo Dose reductionsEarly termination of chemo Enlarged spleenAcute respiratory distress syndromeAnaphylaxisSickle cell disorderBone pain Addition to docetaxel led to significant reduction in grade 3 and 4 neutropenia (P<0.003)No added toxicityMore patients continue on full dose docetaxel for a longer period Neutropenia: An Underserved Market Plinabulin Product Profile Competitive efficacy profileEnhanced safety, including lower incidence of bone pain Plinabulin can be dosed one hour after docetaxel use, unlike G-CSF's 24 hour delay
* Severe Neutropenia Seen After Docetaxel Monotherapy Source: Quartino et al Invest New Drugs 2012; 30:833-845 Neutropenia Is Marked By: Severe InfectionsSepsisHospitalizationsHigh Mortality Cycle 1 Docetaxel Treatment Model Duration of Severe Neutropenia (DSN) refers to the number of days with neutrophil levels below 0.5 x109 cells/LA lower nadir correlates with a longer Duration of Severe Neutropenia (DSN) Day 8 DSN
* Phase 2 Data presented at ASH December 2016 Docetaxel Monotherapy DSN Estimate Model Based on Nadir- Cycle 1 Day 8 Phase 2 Data Supports Favorable Product Profile P < 0.0003 33.3% 4.6% * ~5% Both 20mg and 30mg Plinabulin cohort p-value <0.0003* Planned Phase 3 doseGrade 4/Severe Neutropenia: ANC < 0.5 x 109 cells/L Docetaxel Monotherapy 0 1 2 3 4 Docetaxel + Plinabulin Projected DSN Mean DSN: 1.1 days Mean DSN: 0.065 days 67% 95%
* Efficacy Differentiation: Plinabulin vs. G-CSF Percentage of Patients Experiencing Grade 3 and 4 Neutropenia Percentage of Patients Experiencing Grade 3 and 4 Neutropenia Percentage of Patients Experiencing Grade 3 and 4 Neutropenia Percentage of Patients Experiencing Grade 3 and 4 Neutropenia Percentage of Patients Experiencing Grade 3 and 4 Neutropenia Percentage of Patients Experiencing Grade 3 and 4 Neutropenia Neutropenia Docetaxel100 (n=49)* Docetaxel100+ G-CSF(n=60)** Docetaxel75 (n=55)* Docetaxel75 (n=51)*** Docetaxel75+ Plinabulin(n=81)*** Grade 3/4 85.7% 41% 67.3% 66.7% 11.5% We have not conducted head-to-head trials of G-CSF and Plinabulin in combination with docetaxel for the prevention of docetaxel-induced grade 3 and 4 neutropenia. As a result, the data derived from these separate clinical trials may not be comparable and would not form a basis for marketing Plinabulin, if submitted for regulatory approval.* Shepherd et al J Clin Oncol 2000;18:2095-2103.** Alexopoulos Cancer Chemother Pharmacol 1999;43:25.*** Phase 2 portion of our Phase 1/2 trial described above The above data form the basis of our belief that Plinabulin may be as effective as G-CSF for the prevention of docetaxel-induced grade 3/4 Neutropenia
* Plinabulin: Differentiated from G-CSF in Neutropenia Prevention
* Plinabulin Neutropenia Clinical Program (Study 105) Neulasta 0.6 mg/m2 (n=10) Plinabulin 5 mg/m2 (n=10) Plinabulin 10 mg/m2 (n=10) Plinabulin 20 mg/m2 (n=10) Arm 1Arm 2Arm 3Arm 4 Phase 2 Portion Phase 3 Portion Plinabulin 20 mg/m2* (n=75) *Planned Phase 3 Dose Neulasta 0.6 mg/m2 (n=75) CurrentFirst patient enrolled in US, April 2017 H2 2017First Data Readout H1 2018Interim AnalysisNon-Inferiority H1 2019Final ReadoutNon-Inferiority Study 105 (Docetaxel) Phase 2/3- 200 patients Interim Analysis at n=50/Arm Primary Endpoint: DSN in Cycle 1 Non-Inferiority Margin: 0.65 days
* Neulasta 0.6 mg/m2 (n=20) Plinabulin 10 mg/m2 (n=20) Plinabulin 20 mg/m2 (n=20) Arm 1Arm 2Arm 3 Phase 2 Portion Phase 3 Portion Neulasta 0.6 mg/m2 (n=60) Plinabulin 20 mg/m2 (n=60) *Planned Phase 3 Dose Plinabulin Neutropenia Clinical Program (Study 106) H1 2017Study to Initiate H1 2018 First Data Readout H1 2019Final ReadoutSuperiority Study 106 (TAC) Phase 2/3- 200 patients Final Analysis at n=60/ArmSequential AnalysisPrimary Endpoint: DSN in Cycle 1 Non-Inferiority Superiority First patient enrolled in the US in April 2017
* Indication: Prevention of All Chemo-induced Neutropenia For concurrent administration with a myelosuppressive chemotherapeutic regimen in patients with non-myeloid malignancies for the prevention of chemotherapy induced neutropenia (with Study 105 and 106) Plinabulin's mechanism of action (MOA) is in protecting neutrophils from apoptosis via its immuno-oncology effect (independent of chemotherapy), and has shown to be effective in chemotherapy regimens with different mechanisms in pre-clinical models. As such, we expect Plinabulin's neutropenia reduction effect to be ubiquitous to treatment.Primary Investigator, Dr. Blayney, Stanford Professor, Founding member of NCCN guidelines for neutropenia management TARGET INDICATION
* NSCLC: Large Market Opportunity for Plinabulin Lung cancer is a leading cause of death worldwide~1.8 million diagnoses globally (87% have NSCLC)Nearly 1/3 of global patients are in ChinaDespite multiple approved therapies, the lung cancer treatment market remains fragmented, marked by modest survival benefits, limited by:Effectiveness only in specific tumor mutationsLimited patient response in many patientsUnique safety risks across therapeutic modalitiesPD-1 antibody Drugs are effective in a small percentage of NSCLC patients, typically between 15-30% Plinabulin Target Patient Sub-Groups in 2nd/3rd Line NSCLC 30% Asian10% Western 70% Asian90% Western
* Phase 2 Data: Oral Presentation at ASCO-SITC Meeting (Feb.2017) Durable Response and Extended Survival Benefit of 4.6 Months * We attribute the non-significant P-value to a small number of patients in each treatment arm
* Plinabulin + Nivolumab (PD-1 Antibody) for NSCLC Animal studies provide indications of an immune MOA, which primarily acts through activation and proliferation of tumor antigen-specific CD4 T-cells, a white blood cell active in immune responses. Combo of Plinabulin and PD-1 antibody in immune competent breast cancer model Breast cancer model- Dr. Zippelius Lab at Univ. of Basel U.S. Immuno-Oncology Trial Overview (Investigator Initiated IND)Phase 1/2 study started at UCSDGoal: Efficacy Synergy similar to PD-1+ CTLA-4 Antibodies, but SaferClinical sites: UCSD and Fred HutchinsonPatient: 2nd/3rd line NSCLC Timeline: 2H 2016 initiation, safety and biomarker read-out in 4Q 2017 UCSD Trial Design:28 days per cyclePlinabulin (IV): Day 1, 8, 15Nivolumab (IV): Day 1, 15 Pre-Clinical Clinical
* Plinabulin Clinical Program in Cancer Exploring The Synergy of Plinabulin with Standard of Care Therapies in Multiple Patient Sub-Groups Plinabulin + DocetaxelEGFR wild typePD-1/PD-L1 failed patients includedPhase 3: 550 patients to be enrolled(80% from China) Plinabulin+ PD-1 Antibody*PD-L1+Phase 1/2 study started at UCSD * Combination with Docetaxel in all docetaxel approved indications including NSCLC, gastric cancer, breast cancer, head and neck cancer, and prostate cancer. Potential other chemo combo with Plinabulin. Combination with PD-1/PD-L1 Antibody in PD-1 approved indications including NSCLC, melanoma, renal cancer, Hodgkin's lymphoma, head and neck cancer, and urothelial carcinoma Plinabulin + Docetaxel*RAS MutationsPhase 2 study expected to begin enrollment at UC Davis in 2017
* Seasoned Leadership Team Lan Huang, PhD: Co-Founder, Chairman & Chief Executive OfficerCo-founded clinical CRO Paramax and spearheaded its sale to global CRO RPS, Co-founded Wuxi MTLH Biotech, and sold self-designed peptide drug China rights to Shanghai Pharmaceutical companyBoard member of Oncology Drug Review Board of China Pharma Assoc."Thousand Talent Innovator Award" Drug development recognition from the President of China Ramon Mohanlal, MD, PhD: Executive Vice President; Chief Medical OfficerMore than 20 years experience in strategic drug development, including executive positions at GSK and VertexHead of Established Products Oncology for Novartis G. Kenneth Lloyd, PhD: Chief Scientific OfficerGreater than 45 years experience in Pharma Industry drug discovery and developmentExecutive & Scientific positions at Roche; Synthelabo, Wyeth-Ayerst, SIBIA, and Nereus Gordon Schooley, PhD: Chief Regulatory Officer Executive for more than 20 years leading clinical and regulatory affairsExecutive & Regulatory positions at SkyePharma, Alliance Pharmaceutical and Pacira Pharma Richard Brand, MBA: Chief Financial Officer20 years of investment banking experience and 12 years of institutional investment manager experienceCFO experience in growth companies, including a $6 billion public company
* Unique Access to Large China Market
* China U.S./ Europe Seek broad indication from U.S. FDA in preventing Neutropenia, and in NSCLC in patients with measurable lung lesions Partner with one or more global pharmaceuticals companies for both Neutropenia and NSCLC indications Pursue accelerated development in China for NSCLC indicationBuild an internal sales force for NSCLC indicationRetain a contract sales organization for secondary markets in China Plinabulin Commercial Strategy
* BeyondSpring Inc. (BYSI)-NASDAQ IPO 3/9/2017 IPO & Concurrent Private Placement: $54.3 M ($48 M net)Investors Included:HuaRong, $150 B fund, largest Asset Management Co. in ChinaSangel, top 10 Biotech Focused Fund in China Fosun, $70 B Investment Conglomerate
* Expected Company Milestones 6 Months 12-18 Months 24-30 Months P3 FinalNeutropenia NSCLCIND submission P3 PD-1 ComboBPI-004 [IO]Ubiquitination Technology Platform asset: Fred Hutchinson/UW collaboration P3 InterimNeutropenia NSCLCDataPD-1 ComboIND submission BPI-002 [IO] P2 DataNeutropenia All funded by current cash runway
* Thank You!Contact: Lan Huang, Ph.D.lhuang@beyondspringpharma.comBeyondSpring Inc.28 Liberty Street, 39th Floor, New York, NY 10005Tel: 646-305-6387 | Fax: 646-219-9660
* Robust Patent Estate
* Patients included:2nd/3rd line NSCLC, stage 3b/4n=163 Docetaxel 75mg/m2n=55 Docetaxel 75mg/m2 + Plinabulin 30mg/m2n=50 Docetaxel 75mg/m2n=18 Docetaxel 75mg/m2 + Plinabulin 20mg/m2n=40 Cohort 1: 30mg/m2 Cohort 2: 20mg/m2 Endpoints:Primary: Overall Survival (OS)Safety (includes Neutrophil count) Completed by Nereus - CRO Quintiles; >70% US+ Western Patient Population; Randomized Phase 2 portion of Phase 1/2 trial Plinabulin + Docetaxel in NSCLC: Phase 1/2 Trial
* Plinabulin's Neutropenia Benefit (Cycle 1-4) Plinabulin's Effect in Preventing Grade 4 and Grade 3 Neutropenia is Persistent Grade 3 Neutropenia Cycle 1 Cycle 2 Cycle 3 Cycle 4 Blue: Docetaxel alone (N=73)Red: Docetaxel + Plinabulin (N=90) Grade 4 Neutropenia
* 30 DN(n=50 20 DN (n=40) 20+30 D(n=73 Nausea 48;4 40;0 39;0 Fatigue 52;4 30;3 40;10 Diarrhea 58;8 35;5 33;6 Constipation 36;0 28;0 29;1 Anorexia 34;0 25;3 33;0 Pyrexia 30;0 23;0 26;2 Vomiting 34;4 35;0 25;1 Cough 22;0 33;0 32;0 Alopecia 28;0 25;0 33;0 Dyspnea 22;4 28;5 25;14 Neutropenia 8;8 8;5 33;26 Myalgia 22;2 8;0 19;0 Anemia 24;8 20;5 16;2 Asthenia 8;2 20;13 26;4 Headache 22;0 26;3 11;0 Dizziness 22;0 5;0 9;0 Hypokalemia 20;0 5;5 4;1 Leukopenia 6;2 7;0 12;9 Tachycardia 14;0 7;0 8;0 Arthralgia 14;0 15;0 14;0 Transient Hypertension 32;20 23;5 4;0 Safety Data (Phase 2, NSCLC, Well Tolerated) Common(>=20%) AEs(%Grade 1-4; %Grade 3-4)
* Study 105 Design: Docetaxel Neulasta 0.6 mg/m2 (n=10) Plinabulin 5 mg/m2 (n=10) Plinabulin 10 mg/m2 (n=10) Plinabulin 20 mg/m2 (n=10) Arm 1Arm 2Arm 3Arm 4 Phase 2 Portion Phase 3 Portion Interim Analysis at n=50/Arm Primary Endpoint: DSN in Cycle 1 Non-Inferiority Margin: 0.65 days Plinabulin 20 mg/m2* (n=75) *Current Recommended Phase 3 Dose Docetaxel in patients with NSCLC, breast cancer and prostate cancer Neulasta 0.6 mg/m2 (n=75) Primary EndpointDSN in cycle 1Secondary Endpoints:Incidence of: (1) Grade 4 neutropenia; (2) Febrile Neutropenia; (3) Infection; (4) antibiotic use; (5) docetaxel dose changeIncidence and duration of hospitalization due to Febrile Neutropenia Incidence, occurrence, and severity of bone pain
* Neulasta 0.6 mg/m2 (n=20) Plinabulin 10 mg/m2 (n=20) Plinabulin 20 mg/m2 (n=20) Arm 1Arm 2Arm 3 Phase 2 Portion Phase 3 Portion Final Analysis at n=60/ArmSequential Analysis (DSN cycle 1) Non-Inferiority Superiority Neulasta 0.6 mg/m2 (n=60) Plinabulin 20 mg/m2 (n=60) *Current RP3D Numeric Results for Testing the Difference Between Two Poisson RatesAlternative Hypothesis: Two-Sided Group 1: ControlTest Statistic: Large-Sample Group 2: Treatment Grp 1 Grp 2 Event Event Rate Rate Diff Ratio Power N1 N2 N 1 2 2- 1 2/ 1 Alpha0.90248 53 53 106 1.20 0.60 -0.60 0.5000 0.0500.90051 80 80 160 1.20 0.70 -0.50 0.5833 0.0500.90096 246 246 492 1.20 0.90 -0.30 0.7500 0.050 Statistics for Superiority in Phase 3 Portion Study 106 Design: TAC
* Docetaxel +Plinabulin Plinabulin + Docetaxel Phase 3 Trial for NSCLC Patient Criteria:Patients with at least 1 measurable lung lesionPD-1/PD-L1 antibody failures (stratified)EGFR wild type, mutations not eligible; no restriction on histologyOne prior platinum-based chemotherapy; no restriction on biological therapySAP Plan: KRAS mutant subgroup; PD-L1 expression subgroup; tumor size subgroup; prior treatment include PD-1/PD-L1 or not Patients, n=5502nd/3rd Line NSCLC1:1 Randomization Docetaxel 75mg/m2 Docetaxel 75mg/m2 + Plinabulin 30mg/m2 Endpoints:Primary: Overall SurvivalSecondary: Neutropenia prevention, DOR, QoL Questionnaires, RR, PFS