FWP 1 s001331x11_fwp.htm FWP

Filed Pursuant to Rule 433
Registration Statement No. 333-214610
February 28, 2017
Transformational Science Advancing Oncology

Agenda General Neutropenia Overview Prevention NSCLC BusinessHighlights Summary

General Overview Plinabulin: History • Acquired from Nereus, a discoverycompany, after Phase 1/2 trial inNSCLC indication • Nereus will be issued BeyondSpringshares equal to 10% of fully-dilutedequity capitalization immediatelyprior to IPO Plinabulin: Late Stage • Synthetic analog of the natural Halamide compound in marine micro organisms • Well defined MOA • Late stage candidate in global registrational trials for two indications Multiple Drug Candidates and Management • Fred Hutchinson Cancer Research Center Collaboration • Multiple IO candidates • Seasoned management team supported by industry-leading KOLsand medical advisory board 3

Pipeline Overview Plinabulin Prevention of Neutropenia (in chemo induced Neutropenia) Study 105 (docetaxel) Preclinical Phase 1 Phase 2 Phase 3 Status IND Initiation 1Q 2017 First Data Readout: 2H 2017 Study 106 (TAC) First Data Readout: 1H 2018 NSCLC: Initiation 2Q 2016 Measurable lung tumor Readout: 1Q 2018 (+ Docetaxel) (interim) PD-L1+ Initiation 2H 2016 (+ Nivolumab) Readout: 2017 KRAS Mutant(+ Docetaxel) Metastatic Brain Tumor (+ Radiation) IO Compound BPI-002 (T-cell activation) IO Compound BPI-003 (IKK inhibitor) IO Compound BPI-004 (Neo-Antigen) Fred Hutchinson Collaboration (Ubiquitination technology platform) Note: • All drug candidates are wholly owned Initiation 2017 Initiation 2017 Preclinical Preclinical Preclinical Preclinical 4

Seasoned Leadership Team Lan Huang, PhD: Ramon Mohanlal, G. Kenneth Lloyd, Gordon Schooley, Richard Brand, Co-Founder, MD, PhD: Chief PhD: Chief Scientific PhD: Chief MBA: Chief Chairman & Chief Medical Officer Officer Regulatory Officer Financial Officer Executive Officer • More than 20 years • Greater than 45 years •Executive for more • 20 years of •Co-founded clinical experience in experience in Pharma than 20 years leading investment banking CRO Paramax and strategic drug Industry drug clinical and experience and 12 spearheaded its sale development, discovery and regulatory affairs years of institutional to global CRO RPS, including executive development •Executive & investment manager Co-founded Wuxi positions at GSK and •Executive & Scientific Regulatory positions experience MTLH Biotech, and Vertex positions at Roche; at SkyePharma, • CFO experience in sold self-designed •Head of Established Synthelabo, Wyeth- Alliance growth companies, peptide drug China Products Oncology Ayerst, SIBIA, and Pharmaceutical and including a $6 billion rights to Shanghai for Novartis Nereus Pacira Pharma public company Pharmaceuticalcompany •Board member ofOncology DrugReview Board of China Pharma Assoc. •“Thousand TalentInnovator ward”Drug development recognition from thePresident of China 5

General Neutropenia Overview Prevention NSCLC BusinessHighlights Summary 6

Plinabulin’s Target is Tubulin in Microtubules Cell Cytoskeleton Consists of Polymerized Tubulin a1Tub Immune - Related Anticancer Effects GTP b1Tub GDP Plinabulin Neutrophil Rescue Effects a2Tub Vascular Disruptive Effects b2Tub Wang Y et al. FEBS J. 2016; 283: 102-111 7Singh AV et al. Blood 2011l 117: 5692-5700

Plinabulin’s Detailed Mechanism of ction Plinabulin Rho Activation JNK Activation Immune - Related Anticancer Effects Neutropenia Prevention Effects Dendritic Cell 8

Plinabulin + Docetaxel in NSCLC: Phase 1/2 Trial Completed by Nereus - CRO Quintiles; >70% Western Patient Population; Randomized Phase 2 portion of Phase 1/2 trial Cohort 1: 30mg/m2 Docetaxel 75mg/m2 n=55 Docetaxel 75mg/m2+ Plinabulin 30mg/m2 Patients included: 2nd/3rd line NSCLC, stage 3b/4 n=163 n=50 Cohort 2: 20mg/m2 Docetaxel 75mg/m2 n=18 Docetaxel 75mg/m2+ Plinabulin 20mg/m2 n=40 Endpoints: • Primary: Overall Survival (OS) • Safety (includes Neutrophil count) 9

Severe Neutropenia after Docetaxel Monotherapy Day 8 Cycle 1 DAYS • Severe Infections • Sepsis • Hospitalizations Source: Quartino et al InvestNew Drugs 2012; 30:833-845 • High Mortality 10

Phase 2 Data: Neutrophil Counts in Cycle 1 Day 8 Data of Phase 2 Plinabulin ITT, cohorts 20 mg and 30 mg with lab values  Effect of Plinabulin dose on cycle 1 day 8 Safety (ITT, 20 mg + 30 mg cohorts) Adverse events Sepsis Severe infections Docetaxel dose reduction due to toxicity ** Plinabulin + Docetaxel (DP, n=90) 0 % 0 % 6.7 % Docetaxel (D, n=73) 3.6 % 3.6 % 19.2 % Grade 3 Transient Hypertension n=65 n=39 n=47 Plinabulin 20 mg/m2 vs Docetaxel: p-value < 0.0001Plinabulin 30 mg/m2 vs Docetaxel: p-value < 0.0001Plinabulin 20 mg/m2 vs. 30 mg/m2: p-value = 0.41 * ANC normal range: 2 - 5 x 109 cells/L **Grade 4 neutropenia DP, DP, D arm 20 mg/m2 30 mg/m2 Grade 3 5% 20% 0% Hypertension ***Y axis: unit 109 cells/L 11

Plinabulin + Docetaxel for NSCLC Phase 2 Data: Neutropenia Plinabulin ITT, cohorts 20 mg and 30 mg Cycle 1 Day 8 (Nadir) P < 0.0003* n=65 Grade 4/Severe neutropenia: ANC < 0.5 x 109 cells/L * docetaxel alone vs. Plinabulin + docetaxel n=39 n=47 12

Plinabulin’s Neutropenia Benefit (Cycle 1-4) Plinabulin’s Effect in Preventing Grade 4 and Grade 3 Neutropenia is Persistent 35 30 25 20 15 10 5 0 -5 0 20 Grade 4 Neutropenia Blue: Docetaxel alone (N=73)Red: Docetaxel + Plinabulin (N=90) 40 60 80 100 120 Grade 3 Neutropenia Cycle 1 Cycle 2 Cycle 3 Cycle 4 13

The Lower the Nadir, the Longer the DSN There is a Correlation Between Nadir and Duration of Severe Neutropenia (DSN) Day 8 Neutropenia on Day 8 Grade 4 (severe) Neutropenia is ANC < 0.5 x 109 cells/L, normal levels are 2 x 109 < ANC < 5 x 109 cells/L Based on data published in the Sandoz - FDA Advisory Committee Briefing Document for Zarxio, 2015. 14

Estimated DSN Based on Nadir Day 8 Docetaxel Monotherapy Plinabulin + Docetaxel Mean DSN: 1.1 days Mean DSN: 0.065 days 0 1 2 3 4 Projected DSN 15

Plinabulin Neutropenia Program: Two Studies INDICATION: We are currently conducting clinical trials of Plinabulin for concurrentadministration with a myelosuppressive chemotherapeutic regimen inpatients with non-myeloid malignancies for the prevention of chemotherapyinduced neutropenia. Study 105 Design: Non-Inferiority (Docetaxel) Study Protocol Title (BPI-2358-105): A Phase 2/3, Multicenter, Randomized,Double Blind, Study to Evaluate Duration of Severe Neutropenia (DSN) withPlinabulin Versus Pegfilgrastim in Patients with Solid Tumors ReceivingDocetaxel Myelosuppressive Chemotherapy IND submitted to FDA on Dec. 20, 2016.Study 106 Design: Superiority (TAC) Study Protocol Title (BPI-2358-106): A Phase 2/3, Multicenter, Randomized,Double Blind, Study to Evaluate Duration of Severe Neutropenia (DSN) withPlinabulin Versus Pegfilgrastim in Patients with Breast Cancer ReceivingMyelosuppressive TAC Chemotherapy 16

Study 105 Design: Docetaxel Docetaxel in patients with NSCLC, breast cancer and prostate cancer Arm 1 Arm 2 Arm 3 Arm 4 Phase 2 Portion 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) Phase 3 Portion Neulasta 0.6 mg/m2 (n=77) Plinabulin 20 mg/m2* (n=77) *Current Recommended Phase 3 Dose Primary Endpoint • DSN in cycle 1 Secondary Endpoints:  Incidence of: (1) Grade 4 neutropenia; (2) Febrile Neutropenia; (3) Infection; (4) antibiotic use; (5) docetaxel dose change Incidence and duration of hospitalization due to Febrile Neutropenia Incidence, occurrence, and severity of bone pain Interim Analysis at n=50/Arm  Primary Endpoint: DSN in Cycle 1  Non-Inferiority Margin: 0.65 days 17

Study 106 Design: TAC Arm 1 Arm 2 Arm 3 Phase 2 Portion Neulasta 0.6 mg/m2 (n=20) Plinabulin 10 mg/m2 (n=20) Plinabulin 20 mg/m2 (n=20) Phase 3 Portion Neulasta 0.6 mg/m2 (n=60) Plinabulin 20 mg/m2 (n=60) *Current RP3D Statistics for Superiority in Phase 3 Portion Numeric Results for Testing the Difference Between Two Poisson Rates Final Analysis at n=60/Arm Alternative Hypothesis: Two-SidedTest Statistic: Large-Sample Power N1 N2 N 0.90248 53 53 106 0.90051 80 80 160 0.90096 246 246 492 Group 1: ControlGroup 2: Treatment Grp 1 Grp 2 Event Event Rate Rate Diff Ratio λ1 λ2 λ2-λ1 λ2/λ1 Alpha 1.20 0.60 -0.60 0.5000 0.050 1.20 0.70 -0.50 0.5833 0.050 1.20 0.90 -0.30 0.7500 0.050 Sequential Analysis(DSN cycle 1) Non-InferioritySuperiority 18

Plinabulin Prevents Multiple Chemo’s Neutropenia in Rat Neutropenia model Docetaxel Effect of Plinabulin on Docetaxel-Induced Neutropenia in Rat Blood 48 h. post Dosing (Docetaxel 1 h. prior to Plinabulin) p= 0.0355; n=5 per group 1.50 1.25 1.00 0.75 0.50 0.25 0.00 Cyclophosphamide Effect of Plinabulin on Cyclophosphamide-Induced Neutropenia in Rat Blood 48 h. post Dosing (Cyclophosphamide 1 h. prior to Plinabulin) p= 0.0494; n=5 per group 2.75 2.50 2.25 2.00 1.75 1.50 1.25 1.00 0.75 0.50 0.25 0.00 19

Plinabulin NDA Data Package Plinabulin Compared to G-CSF Development Plan: • Indication for use: Prevention of chemotherapy induced neutropenia • Same primary efficacy: Duration of Severe Neutropenia (DSN) in Cycle 1 • Near identical clinical study designs • Similar sample sizes Clinical Data Summary Section: • BPI-2358-105: Non-inferior DSN to Neulasta (docetaxel moderate Neutropenia) • BPI-2358-106: Superior DSN to Neulasta (TAC severe Neutropenia) • Safety database includes studies 105 and 106 and NSCLC P1, P2, and P3 20

Product Differentiation: Plinabulin vs. G-CSF Neutropenia Market $7.3 Billion Globally in 2015 Percentage of Patients Experiencing Grade 3 and 4 Neutropenia† Docetaxel 100 Neutropenia (n=49)* Docetaxel Docetaxel 100 75+ G-CSF (n=60)** (n=55)* Docetaxel Docetaxel 75 75 + Plinabulin(n=51)*** (n=81)*** Grade 3/4 85.7% 41% 67.3% 66.7% 11.5% 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 † 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 becomparable and would not form a basis for marketing Plinabulin, if approved. * 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 21

Plinabulin: Differentiated from G-CSF in Neutropenia Prevention In 2015 Chemo-Induced Neutropenia was a $7.3 Billion Market G-CSF Bone pain in > 20% of patients Administered 24 hours after chemo G-CSF biologics/biosimilars mostlyused in the high risk FN segment and limited in use by side effects Plinabulin Bone pain in < 4% of patients Can be dosed 1 hour after chemo Small molecule alternative withpotential to be used in lower risk FN segments due to lower side-effect profile 22

Near Term Opportunity: Neutropenia Study 105 (Docetaxel) Phase 2/3 Q1 2017 H2 2017 H1 2018 H1 2019 Study Initiated First Data Readout Interim Analysis Final Readout Non-Inferiority Non-Inferiority Study 106 (TAC) Phase 2/3 H1 2017 H1 2018 H1 2019 Study Initiated First Data Readout Final Readout Superiority 23

General Neutropenia Overview Prevention NSCLC BusinessHighlights Summary 24

Plinabulin Anti-cancer MOA: Immune-Enhancing and Apoptosis Cancer Cells Tumor Antigen Tumor Killing HMCII  RhoB .. Dendritic Cell CD80 Plinabulin Cancer CellApoptosis TubulinGEF-H1JNK-ActivationC-Jun Caspase-3 Activation CD86 o-Stimulation T-Cell Activation T-Cell TRIF-GEFH1-RhoB pathway is involved in MHCII Expression on dendritic cells that is critical for CD4T cell activation, Kamon et al. EMBO J. 25: 4108-19 (2006) Heasman et al. Coordinated RhoA signaling at the leading edge and uropod is required for T cell transendothelial migration. J cell Biol. 190: 553-563 (2010). 25

Phase 2 Anti-Cancer Activity Data Review: NSCLC Encouraging Activity in Measurable Lung Lesion Oral Presentation at ASCO-SITC: Durable Response and Extended Survival Benefit of 4.6 Months Plinabulin Docetaxel + Docetaxel alone (DN) (D) N=38 N=38 11.3 M 6.7 M mOS P = 0.29 ORR 18.4% 10.5% 26

NSCLC: Phase 3 Trial Design Patient Criteria: • Patients with at least 1 measurable lung lesion • PD-1/PD-L1 antibody failures (stratified) • EGFR wild type, mutations not eligible; no restriction on histology • One prior platinum-based chemotherapy; no restriction on biological therapy • SAP Plan: KRAS mutant subgroup; PD-L1 expression subgroup; tumor size subgroup; prior treatment include PD-1/PD-L1 or not Docetaxel 75mg/m2 Patients, n=5502nd/3rd Line NSCLC1:1 Randomization Docetaxel 75mg/m2+ Plinabulin 30mg/m2 Docetaxel + Plinabulin Endpoints: • Primary: Overall Survival • Secondary: Neutropenia prevention, DOR, QoL Questionnaires, RR, PFS 27

Neutropenia Results in Phase 3 NSCLC Trial Phase 3 NSCLC Trial Confirming Neutropenia Results on a Prospective Basis 28

Clinical Program of Plinabulin in NSCLC Efficacy Synergy of Plinabulin with Standard of Care Therapies Plinabulin+ Docetaxel* • PD-L1- in 2nd Line (50%) • PD-1/PD-L1 failed patients in 3rd line (80%) Phase 3: 550 patients to be enrolled Goal: Efficacy Synergy and Better Safety Plinabulin + PD-1 Antibody** • PD-L1+ Phase 1/2 studystarted at UCSD Goal: Efficacy Synergysimilar to PD-1+ CTLA-4 Antibodies, but Safer * Combination with Docetaxel in all docetaxel approved indications including NSCLC, gastric cancer, breast cancer, head and neck cancer, and prostate cancer ** Combination with PD-1/PD-L1 AB in PD-1 approved indications including NSCLC, melanoma, renal cancer, Hodgkin’s lymphoma, head and neck cancer, and urothelial carcinoma 29

NDA Plan for NSCLC Current Q1 2018 Q1 2019 550 patients to be Interim Analysis Final Analysis enrolled 30

General Neutropenia Overview Prevention NSCLC BusinessHighlights Summary 31

Uniquely Positioned to Access to Large China Market Plinabulin is eligible for category 1 new drug approval in China, which will accelerate NDA review process and present the opportunity for early launch in China: • Innovative drug not approved elsewhere • Will manufacture in China for China market • Received Phase 3 CTA from the CFDA • BeyondSpring CEO status as “Thousand Talent Innovator ward” allows additional expedited approval High approval rate of category 1 oncology drugs developed by Chinese companies after receiving Phase 3 CTA: • e.g. Icotinib (Betta Pharma) and Chidamide (Chipscreen) 32

Financial Overview Utilizing existing and anticipated cash to pursue clinical developmentplan through 2017 • Continuance of Plinabulin + docetaxel Phase 3 for NSCLC • Completion of Plinabulin + nivolumab Phase 1/2 for NSCLC • Begin first registrational trial Plinabulin + chemo for prevention of neutropenia Use of IPO Proceeds • Completion of Plinabulin + docetaxel Phase 3 for NSCLC • Continuance Phase 2/3 trials Plinabulin + chemo for prevention of neutropenia • Phase 2 trial of Plinabulin + nivolumab for NSCLC • Other pipeline assets 33

Company Catalysts 24-30 Months 6 Months P2 Data • Neutropenia 12-18 Months P3 Interim • Neutropenia • NSCLC Data • PD-1 ComboIND submission • BPI-002 [IO] P3 Final • Neutropenia • NSCLC IND submission • P3 PD-1 Combo • BPI-004 [IO] • Fred Hutchinson collaboration asset 34

General Neutropenia Overview Prevention NSCLC BusinessHighlights Summary 35

Summary Focused on developing novel therapies to treat multiple oncology indications Multiple near term catalysts for Plinabulin Efficient US / Chinaclinical development strategy Robust pipeline Strong management team • Multinational Phase 3 trial for NSCLC • Phase 2/3 trials for prevention of chemo induced Neutropenia • Phase 1/2 combination immunotherapy trial for NSCLC • Potential for accelerated clinical development • Fast Track regulatory path for NSCLC and market access in China • Scalable model for pipeline assets • Multiple follow-on indications for Plinabulin • Next-generation immuno-oncology assets • Multiple new products from Fred Hutchinson/UW collaboration • Seasoned management team supported by KOLs and medical advisory board 36

Thank You! Lan Huang, Ph.D. lhuang@beyondspringpharma.com BeyondSpring Inc. 28 Liberty Street, 39th Floor, New York, NY 10005 Tel: 646-305-6387 | Fax: 646-219-9660 37

Addendum 38

Additional Assets Fred Hutchinson Collaboration • Fred Hutchinson will provide up to six new projects per year for five yearsas potential ground-breaking cancer treatment or diagnostics options forlicense to BeyondSpring. • Ubiquitination Technology: One approach is using a “molecular glue” tobind ubiquitin ligase to the target E3 ligase for oncogenes; collaboratingwith Dr. Zheng, HHMI Investigator, University of Washington. IO - Internal Assets • BPI-002: A small molecule co-stimulation agent that activates CD4 and CD8T cells; can be alternative to CTLA-4 inhibitors, when combined with PD1/PD-L1 inhibitors. • BPI-004: A small molecule that induces neoantigens (immunogens) in tumors that previously were not immunogenic. More than 50% of humancancers are not immunogenic and therefore do not respond to PD1/PD-L1inhibitors. By making these tumors immunogenic with BPI-004, thesecancers become responsive to PD1/PD-L1 inhibitors. 39

Robust Patent Estate 72 grantedComposition and Usage Patents forPlinabulin in 34 countriesthrough 2025 5 additional US provisional global patent applications pending with the potentialfor protection to 2036 Composition of matter patent to 2025 (up to 2030 with possible patent term extension) 40

Safety Data (Phase 2, NSCLC, Well Tolerated) Common (>=20%) AEs (% Grade 1-4;% Grade 3-4) 30 D (n=55） 30 DP (n=50） 20 D (n=18） 20 DP (n=40) Nausea 44;0 48;4 22;0 40;0 Fatigue 40;11 52;4 39;6 30;3 Diarrhea 33;4 58;8 33;11 35;5 Constipation 33;0 36;0 17;6 28;0 Anorexia 31;0 34;0 39;0 25;3 Pyrexia 29;2 30;0 17;0 23;0 Vomiting 22;0 34;4 33;6 35;0 Cough 33;0 22;0 28;0 33;0 Alopecia 29;0 28;0 44;0 25;0 Dyspnea 24;13 22;4 28;17 28;5 Neutropenia 36;27 8;8 22;22 8;5 Myalgia 22;0 22;2 11;0 8;0 Anemia 16;2 24;8 17;0 20;5 Asthenia 26;4 8;2 28;6 20;13 Headache 9;0 22;0 17;0 26;3 Dizziness 6;0 22;0 17;0 5;0 Hypokalemia 2;1 20;0 11;0 5;5 Leukopenia 9;5 6;2 22;22 7;0 Tachycardia 4;0 14;0 22;0 5;0 Arthralgia 11;0 14;0 22;0 15;0 Transient 4;0 32;20 6;0 23;5 Hypertension 41

Study 105 Design: Docetaxel Docetaxel in patients with NSCLC, breast cancer and prostate cancer Arm 1 Arm 2 Arm 3 Arm 4 Phase 2 Portion 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) Phase 3 Portion Neulasta 0.6 mg/m2 (n=77) Plinabulin 20 mg/m2* (n=77) *Current Recommended Phase 3 Dose Statistics for Non-Inferiority in Phase 3 Portion Interim Analysis at n=50/Arm Power N1 N2 N Mean1 Mean2 S1 S2 Alpha 0.84923 77 77 154 0.600 1.000 0.60 1.00 0.025 Details when Spending = O'Brien-Fleming, N1 = 77, N2 =77, S1 = 0.60, S2 = 1.00, Diff = -0.400 Lower Upper Nominal Inc Total Inc Total Look Time Bndry Bndry Alpha Alpha Alpha Power Power 1 0.65 2.54692 0.005 0.005 0.005 0.45210 0.452 2 1.00 1.98958 0.023 0.020 0.025 0.39713 0.849 Non-Inferiority margin 0.65 days Primary Endpoint: DSN incycle 1 42

Plinabulin + Nivolumab for NSCLC Pre-Clinical Animal studies provide indications of an immuneMOA, which primarily acts through activation andproliferation of tumor antigen-specific CD4 T-cells,a white blood cell active in immune responses. Combo of Plinabulin and PD-1 antibody in immunecompetent breast cancer model Breast cancer model - Dr. Zippelius Lab at Univ. of Basel Clinical U.S. Immuno-Oncology Trial Overview (Investigator Initiated IND) • Clinical sites: UCSD and Fred Hutchinson • Patient: 2nd/3rd line NSCLC • Timeline: 2H 2016 initiation, safety and biomarker read-out in 4Q 2017 UCSD Trial Design: • 28 days per cycle • Plinabulin (IV): Day 1, 8, 15 • Nivolumab (IV): Day 1, 15 43