GEF-H1

New Clinical Data from MD Anderson Presented at the Society for Immunotherapy of Cancer’s 38th Annual Meeting80% DCR (disease control rate) in non-radiated tumor with Durable Responses in Heavily Pretreated Patients in 6 different cancersFull data was presented at SITC’s 38th Annual Meeting; The Company will host a call at 8:30 a.m. ET today. Dial in: 877-407-0792, conference title: Clinical Significance of Plinabulin SITC Presentation with PI Dr. Steven Lin from MD Anderson NEW YORK, Nov. 07, 2023 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (NASDAQ: BYSI) (“BeyondSpring” or the “Company”), a global clinical-stage biopharmaceutical company focused on using a groundbreaking technology platform for drug discovery and developing innovative therapies to improve clinical outcomes for patients with high unmet medical needs, today announced new data that translates preclinical proof-of-concept to clinical evidence of plinabulin’s immunomodulating activity. BeyondSpring and MD Anderson presented the data at the Society for Immunotherapy of Cancer's (SITC) 38th Annual Meeting on Nov 4th in San Diego, CA on an open-label, Phase 1 basket study at The University of Texas MD Anderson Cancer Center in cancer patients after progressing on PD-1, PD-L1 and/or CTLA-4 antibodies (NCT04902040) in six cancer types. Based on preclinical models, where plinabulin plus radiation and anti-PD-1 antibody enhances dendritic cell (DC) activation, T-cell proliferation, and abscopal effect, a clinical study was initiated to test these findings. At the Phase 1 data cut-off (August 31, 2023), 19 heavily pretreated patients with 6 different cancers were exposed to plinabulin (30 mg/m2) after radiation initiation to an amendable lesion (3-6 hours apart) plus anti-PD-1 antibody, including pembrolizumab or nivolumab. 11 out of 14 patients eligible for efficacy assessment per RECIST criteria and had measurable target lesion responses in the non-irradiated tumor lesion. Disease control rate evaluates the tumor reduction in non-irradiated tumor to assess abscopal effect from immune agents. 80% DCR (disease control rate) in non-irradiated tumor: In 10 immunotherapy-refractory patients of 6 different cancers (Hodgkin Lymphoma, NSCLC, SCCHN, Merkel Cell Carcinoma, RCC, Fibrolamellar HCC), plinabulin triple combination is safe and yields encouraging response with 80% disease control rate (3 PR, 5 SD, 2 PD).Durable Response in heavily pre-treated patients: 2 Hodgkin’s lymphoma patients who progressed after 12 or 16 prior lines of therapy respectively, had durable responses with one PR and one SD. These patients continued treatment after data cutoff.DC maturation in responding patients: Plinabulin administered after radiation initiation induces an early systemic immune response (detectable 3 days later) in subsets of peripheral blood DC and monocytes in patients with clinical benefits (PR+SD).Plinabulin mediates GEF-H1-dependent immune activation in responding patients: In patients with PR+SD, tumor scRNAseq analysis indicates GEF-H1-dependent immune activation in subsets of DC and monocyte-derived macrophages. Such activation was not seen in patients with PD.Additional biomarker analyses at baseline and post-treatment are underway. “There are severe unmet medical needs for cancer patients who progress on immunotherapies. We have been studying Plinabulin for 6 years, starting from preclinical proof-of-concept work in showing its DC maturation, abscopal effect and selective sequencing benefit with radiation, presented at the 2020 AACR meeting, and now the successful clinical translation in the triple IO regimen and its notable high disease control rate in these hard-to-treat and multiple refractory cancers,” Dr. Steven H. Lin, MD/PhD, professor of radiation oncology at MD Anderson commented. “These results are encouraging but preliminary. Based on the consistent mechanism in DC maturation in responding patients, this sets the stage for additional clinical studies of plinabulin/IO combinations in IO-refractory settings in a number of indications, including NSCLC and Hogkins Lymphoma.” SITC Conference Abstract Number: 732Title: Immune Activation with Plinabulin Enhances Anti-tumor response Combining Radiation with Immune Checkpoint BlockadePresenter: Steven H. Lin, MD/PhDSession: Poster Hall Phase 1 Study RegimenAll subjects received a triple combo treatment of Radiation Therapy (RT) + Plinabulin + Pembrolizumab or Nivolumab in Cycle 1, followed by the same anti-PD-1 antibody and plinabulin combo regimen in Cycle 2 and beyond until disease progression or development of unacceptable toxicity, withdrawal from study treatment, or discontinuation of this study. A short course of local consolidative RT was administered in Cycle 1 starting from Day 1. Optional sequential RT may have been administered to target other untreated lesions at discretion of the treating doctor in Cycle 2 of any regimens.Plinabulin was dosed on Day 1 and Day 4 of Cycle 1 of any anti-PD-1 regimen, and if optional RT was given in Cycle 2, Plinabulin was also given on Day 4 of Cycle 2. Plinabulin was given on Day 1 of Cycle 3 and thereafter. Anti-PD-1 antibody was dosed on Day 1 of every treatment cycle (also on Day 15 [Q4W] in case of regimen containing Nivolumab as Anti-PD-1 mAb).Subjects received the same anti-PD-1/PD-L1 mAb they failed in the prior treatment. Conference Call and Webcast InformationBeyondSpring will host a conference call and webcast today at 8:30 a.m. Eastern Time. The dial in numbers for the conference call are 1-877-407-0792 (U.S.) or 1-201-689-8263 (international). Please reference conference title: Clinical Significance of Plinabulin SITC Presentation with PI Dr. Steven Lin from MD Anderson. A live webcast will be available on BeyondSpring’s website at www.beyondspringpharma.com under “Events & Presentations” in the Investors section. An archived replay of the webcast will be available for 30 days. About BeyondSpringBeyondSpring (NASDAQ: BYSI) is a global clinical-stage biopharmaceutical company focused on developing innovative therapies to improve clinical outcomes for patients with high unmet medical needs. The Company is advancing its first-in-class lead asset, Plinabulin, as a direct anti-cancer agent in various cancer indications and to prevent chemotherapy-induced neutropenia. Its pipeline also includes three preclinical immuno-oncology assets. Additionally, BeyondSpring’s subsidiary, SEED Therapeutics, leverages a proprietary targeted protein degradation (TPD) drug discovery platform and has an initial R&D collaboration with Eli Lilly. Learn more by visiting https://beyondspringpharma.com. Investor Contact:IR@beyondspringpharma.com Media Contact:PR@beyondspringpharma.com

Additional analyses of non-small cell lung cancer (NSCLC) studies support the efficacy of plinabulin monotherapy in reducing the mean duration of severe neutropenia (DSN) for patients receiving docetaxelIn an analysis of breast cancer patients, plinabulin monotherapy was superior vs no treatment for docetaxel-induced neutropenia and hematologic complications NEW YORK, Dec. 13, 2022 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (the “Company” or “BeyondSpring”) (Nasdaq: BYSI), a clinical stage global biopharmaceutical company focused on developing innovative cancer therapies, today announced data from the ESMO Asia Congress 2022 and the American Society of Hematology (ASH) Annual Meeting about the use of lead asset, plinabulin, for the prevention of docetaxel-induced neutropenia (DIN) in non-small cell lung cancer (NSCLC) patients. In addition, data was presented on plinabulin for the prevention of docetaxel-induced neutropenia in breast cancer (BC in the 105 study) at the 2022 San Antonio Breast Cancer Symposium (SABCS). The analyses in the NSCLC studies support the efficacy of plinabulin as a monotherapy in reducing the mean duration of severe neutropenia (DSN) with a >1 day benefit for patients receiving docetaxel and plinabulin (compared to patients not receiving plinabulin) in two independent randomized trials (study 101 and 103). “Docetaxel-induced neutropenia can cause life-threatening infections in cancer patients, and the current standard of care, prophylactic treatment with a G-CSF in high-risk patients, has limitations. It has to be administered 24 hours following chemotherapy, and patients can experience post-treatment bone pain, a mild reduction in platelet count and a decline in quality of life,” said Dr. Douglas Blayney, professor of medicine (oncology) emeritus at Stanford University Medical School and global principal investigator for the plinabulin neutropenia prevention studies. “The data that we presented at these three conferences demonstrate that plinabulin can provide solutions for some of the challenges seen with G-CSF. Plinabulin is given on the same day as chemotherapy as a short infusion, has minimal associated bone pain, no reduction in platelet count and quality of life is maintained throughout the course of therapy. Importantly, the analyses showed a reduction in mean DSN of one day or more in NSCLC patients receiving plinabulin vs placebo (no G-CSF), which is the gold standard for regulatory review.” Trials Mentioned in the Abstracts study 101: Phase 2 study of plinabulin and docetaxel (75 mg/m2) vs. docetaxel alone (75 mg/m2) in 2nd/3rd line NSCLC (NCT00630110)study 103: Phase 3 study of plinabulin and docetaxel (75 mg/m2) vs. docetaxel alone (75 mg/m2) in 2nd/3rd line NSCLC (NCT02504489)study 105: Phase 2/3 study of plinabulin vs. pegfilgrastim with docetaxel (75 mg/m2) treatment in NSCLC, breast cancer and prostate cancer (NCT03102606) Poster Presentation at the ASH Annual Meeting Title: Prevention of Docetaxel (Doc)-Induced Neutropenia (DIN) with Single Agent Plinabulin (Plin) Versus (vs) Control (No-Treatment or Placebo) in Non-Small Cell Lung Cancer (NSCLC) in Two Randomized TrialsPresentation Number: 1094 Presenter: Dr. Douglas Blayney, professor of medicine (oncology) emeritus at Stanford University Medical School and global principal investigator for the plinabulin neutropenia prevention studies The presentation summarized data from two randomized NSCLC studies (study 101 and 103), and DIN results were compared between the plinabulin arm and the control arm (placebo or no treatment). The DSN was calculated based on Day 8 absolute neutrophil count (ANC) values in the plinabulin and control arms. In NSCLC patients, docetaxel 75 mg/m2 is typically used without G-CSF prophylaxis (“no treatment”). This analysis focuses on the effectiveness of plinabulin (20 mg/m2 or its pharmacokinetic equivalent exposure) vs. control for the prevention of DIN in the 101 and 103 studies.In summary, in these two independent randomized studies, plinabulin demonstrated a superior benefit for Gr4N, Gr3/4N, all GrN and DSN compared to the control. Importantly, in both these randomized studies, there was a reduction in mean DSN of >1 day for plinabulin vs. control. Oral Presentation at ESMO Asia Congress 2022 Title: Superior single agent effectiveness with plinabulin (Plin) versus (vs) placebo (Plac) for docetaxel (Doc)-induced neutropenia (DIN) prevention in non-small cell lung cancer (NSCLC) patients (pts)Presentation Number: 276MO Presenter: Dr. Douglas Blayney, professor of medicine (oncology) emeritus at Stanford University Medical School and global principal investigator for the plinabulin neutropenia prevention studies The presentation summarized DIN data from a non-randomized comparison derived from two different studies: plinabulin data from study 105 and the control (placebo or no treatment) data from study 103. In the 105 study, NSCLC pts with at least one febrile neutropenia (FN) risk factor received docetaxel 75 mg/m2 with plinabulin (20 mg/m2 or its equivalent of 40 mg fixed dose, n=30).In the 103 study, patients received docetaxel 75 mg/m2 without plinabulin (placebo; n=224).In summary, plinabulin was superior for the prevention of DIN and hematologic complications vs control: Grade 4 Neutropenia: 17% with plinabulin vs 40% with placebo (p-value=0.02). In addition, the mean DSN was 0.43 days for plinabulin vs. 1.32 days for placebo (p-value=0.002). There was also a favorable quality of life and safety profile with plinabulin. Poster Presentation at SABCS Title: Superior effectiveness of Plinabulin (Plin) versus no-treatment for Docetaxel (Doc)-induced neutropenia (N) and other hematologic complication in breast cancer (BC) patientsPresentation Number: P1-12-10 Presenter: Dr. Douglas Blayney, professor of medicine (oncology) emeritus at Stanford University Medical School and global principal investigator for the plinabulin neutropenia prevention studies The presentation summarized DIN data for plinabulin from study 105 and the control data (placebo or no treatment) was taken from the literature. The hematologic complications endpoints from the 27 early breast cancer patients with at least one NCCN high FN risk factor (N=27) from the Phase 3 portion of 105 study were compared with the no-treatment studies from literature where patients were given 75 mg/m2 docetaxel without G-CSF (Harvey et al., JCO, 2006 and Dieras et al., Br J Ca, 1996). Blood sampling in the no-treatment studies (Harvey and Dieras) were infrequent and likely underestimated the true grade 4 neutropenia frequency.In summary, despite a higher frequency of ANC sampling in cycle 1, plinabulin was superior vs no-treatment for DIN and hematologic complications. Quality of life was maintained, and there were minimal adverse effects including minimal bone pain burden in the plinabulin arm vs. no-treatment. About Plinabulin Plinabulin, BeyondSpring’s lead asset, is a selective immunomodulating microtubule-binding agent, which is a potent antigen presenting cell (APC) inducer that is being developed as an anticancer agent. Plinabulin triggers the release of the immune defense protein, GEF-H1, which leads to two distinct effects: first is a durable anti-cancer benefit due to the maturation of dendritic cells resulting in the activation of tumor antigen-specific T-cells to target cancer cells and the second is a CIN prevention benefit. Plinabulin has single agent anti-cancer activity in a number of cancers including small cell lung cancer (SCLC) and multiple myeloma (MM). Plinabulin also exerts early-onset of action in the prevention of chemotherapy-induced neutropenia (CIN) by boosting the number of hematopoietic stem/progenitor cells (HSPCs). About BeyondSpringHeadquartered in New York City, BeyondSpring is a clinical stage global biopharmaceutical company focused on developing innovative cancer therapies to improve clinical outcomes for patients who have high unmet medical needs. BeyondSpring’s first-in-class lead asset, plinabulin, is being developed as a potential “pipeline in a drug” in various cancer indications as a direct anti-cancer agent and to prevent chemotherapy-induced neutropenia (CIN). The plinabulin and G-CSF combination for the prevention of CIN has demonstrated positive Phase 3 data in the PROTECTIVE-2 study. In the DUBLIN-3 study, a global, randomized, active controlled Phase 3 study, the plinabulin and docetaxel combination met the primary endpoint of extending overall survival compared to docetaxel alone in 2nd/3rd line non-small cell lung cancer (NSCLC) (EGFR wild type). Additionally, plinabulin is being broadly studied in combination with various immuno-oncology regimens that could boost the efficacy of PD-1/PD-L1 antibodies in seven different cancers. Lastly, BeyondSpring’s pipeline includes three preclinical immuno-oncology assets and a subsidiary, SEED Therapeutics, which is leveraging a proprietary targeted protein degradation drug discovery platform with initial R&D collaboration with Eli Lilly. Investor Contact:IR@beyondspringpharma.comMedia Contact:PR@beyondspringpharma.com

Plinabulin rapidly (within 24 hours) mitigates chemotherapy-induced myelosuppression by protecting bone marrow granulocyte-monocyte progenitor (GMP) stem cellsNEW YORK, Sept. 13, 2022 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (the “Company” or “BeyondSpring”) (NASDAQ: BYSI), a clinical stage global biopharmaceutical company focused on developing innovative cancer therapies to improve clinical outcomes for patients who have a high unmet medical need, today announced data from a poster presentation at the ESMO Congress 2022 being held September 9-13, 2022, in Paris, France. The poster includes a new analysis from the Phase 2/3 PROTECTIVE-1 (NCT03102606) and PROTECTIVE-2 (NCT03294577) trials. The data provides evidence of protection of bone marrow granulocyte-monocyte progenitor (GMP) stem cells within 24 hours after chemotherapy based on an evaluation of peripheral immature and mature neutrophil counts. “We’re pleased to present mechanistic data demonstrating the effectiveness of plinabulin for the prevention of chemotherapy-induced neutropenia (CIN). The acceptance of this data by ESMO provides continued validation of our CIN program and how plinabulin can complement the current standard of care,” said Dr. Douglas Blayney, professor of medicine at Stanford University Medical School and global principal investigator for the CIN studies. “We’ve known for a while that there is a ‘gap’ in the first week of a chemotherapy cycle where G-CSF isn’t effective, and patients are left vulnerable to CIN and potentially life-threatening infections. This study shows how plinabulin has a mechanism of action (MOA) that can act within the first 24 hours by increasing the number of important cell types that can protect against potential infection. Plinabulin has continuously demonstrated how it can be a novel tool in the oncologist’s arsenal to potentially improve outcomes for these patients.” Poster Presentation Details Title: Clinical Evaluation of Plinabulin’s Granulocyte-Monocyte Progenitor (GMP) Stem Cell Effects for the Prevention of Chemotherapy-Induced Neutropenia (CIN)Presentation #: 1588PPresenter: Dr. Douglas Blayney, professor of medicine at Stanford University Medical School and global principal investigator for the CIN studies Peripheral blood counts for mature (segmented) and immature neutrophils, white blood cells (WBCs), red blood cells (RBCs) and platelets were obtained from LabCorp. The blood counts were analyzed before and 24 hours after chemo administration without (control; N=198) or with plinabulin (N=298).The absolute neutrophil count (ANC) with and without plinabulin was comparable at pre-dose C1D1 (p=0.96) but was significantly higher at 24 hours post-chemo dose with plinabulin vs. control (p<0.0001). At 24 hours post-chemo dose, the mean ANC had increased by 3.2 x 109/L with plinabulin (p<0.0001) whereas the mean ANC had decreased by 0.55 x 109/L with the control (p=0.018) due to the myelosuppressive effect of TAC chemotherapy.Pre-dose (C1D1), the proportion of patients with a GMP-derived immature cell count value >0 was ~0 for both the plinabulin and control arms. At 24 hours post-chemo, the number of patients with an immature neutrophil count >0 had significantly increased with plinabulin but not with the control (shown in the table below). The proportion of patients with immature cells from all other WBCs and RBCs was ~0 at pre- or post-chemo dose with or without plinabulin. Proportion of patients with these GMP-derived immature cells:Pre-dose C1D1 plinabulin N (%)Pre-dose C1D1 control N (%)p-value24 hours post-plinabulin N (%)24 hours post-control N (%)p-valuePromyelocytes0 (0)0 (0)NA2 (0.7)0 (0)0.25Myelocytes1 (0.4)1 (0.5)0.823 (7.7)0 (0)<0.0001Metamyelocytes1 (0.4)1 (0.5)0.820 (6.7)0 (0)0.0002Bands11 (3.7)9 (4.5)0.621 (7.0)2 (1.0)0.0017 Dr. Ramon Mohanlal, executive vice president of research and development and chief medical officer at BeyondSpring Pharmaceuticals, added, “Plinabulin, given as a single dose per cycle, has differentiated properties compared to G-CSF, such as a same-day-dosing schedule, no significant bone pain and a rapid onset MOA (within 24 hours), which provides a strong basis for its continued development in CIN prevention. It’s been an honor to work with Dr. Blayney and our team at BeyondSpring to unpack the nuances of what makes plinabulin different from what’s currently available for providers and patients. Plinabulin is a unique novel agent with both CIN prevention and anti-cancer properties. We look forward to sharing further analyses in the CIN program as well as continuing to progress on our work with plinabulin as a potential treatment for non-small cell lung cancer.” About PlinabulinPlinabulin, BeyondSpring’s lead asset, is a selective immunomodulating microtubule-binding agent, which is a potent antigen presenting cell (APC) inducer that is being developed as an anticancer agent. Plinabulin triggers the release of the immune defense protein, GEF-H1, which leads to two distinct effects: first is a durable anti-cancer benefit due to the maturation of dendritic cells resulting in the activation of tumor antigen-specific T-cells to target cancer cells and the second is a CIN prevention benefit. Plinabulin has single agent anti-cancer activity in a number of cancers including small cell lung cancer (SCLC) and multiple myeloma (MM). Plinabulin also exerts early-onset of action in the prevention of chemotherapy-induced neutropenia (CIN) by boosting the number of hematopoietic stem/progenitor cells (HSPCs). About BeyondSpring Headquartered in New York City, BeyondSpring is a clinical stage global biopharmaceutical company focused on developing innovative cancer therapies to improve clinical outcomes for patients who have high unmet medical needs. BeyondSpring’s first-in-class lead asset, plinabulin, is being developed as a potential “pipeline in a drug” in various cancer indications as a direct anti-cancer agent and to prevent chemotherapy-induced neutropenia (CIN). The plinabulin and G-CSF combination for the prevention of CIN has demonstrated positive Phase 3 data in the PROTECTIVE-2 study. In the DUBLIN-3 study, a global, randomized, active controlled Phase 3 study, the plinabulin and docetaxel combination met the primary endpoint of extending overall survival compared to docetaxel alone in 2nd/3rd line non-small cell lung cancer (NSCLC) (EGFR wild type). Additionally, plinabulin is being broadly studied in combination with various immuno-oncology regimens that could boost the efficacy of PD-1/PD-L1 antibodies in seven different cancers. Lastly, BeyondSpring’s pipeline includes three preclinical immuno-oncology assets and a subsidiary, SEED Therapeutics, which is leveraging a proprietary targeted protein degradation drug discovery platform. Cautionary Note Regarding Forward-Looking StatementsThis press release includes forward-looking statements that are not historical facts. Words such as “will,” “expect,” “anticipate,” “plan,” “believe,” “design,” “may,” “future,” “estimate,” “predict,” “objective,” “goal,” or variations thereof and variations of such words and similar expressions are intended to identify such forward-looking statements. Forward-looking statements are based on BeyondSpring’s current knowledge and its present beliefs and expectations regarding possible future events and are subject to risks, uncertainties and assumptions. Actual results and the timing of events could differ materially from those anticipated in these forward-looking statements as a result of several factors including, but not limited to, difficulties raising the anticipated amount needed to finance the Company’s future operations on terms acceptable to the Company, if at all, unexpected results of clinical trials, delays or denial in regulatory approval process, results that do not meet the Company’s expectations regarding the potential safety, the ultimate efficacy or clinical utility of our product candidates, increased competition in the market, and other risks described in BeyondSpring’s most recent Form 20-F on file with the U.S. Securities and Exchange Commission. All forward-looking statements made herein speak only as of the date of this release and BeyondSpring undertakes no obligation to update publicly such forward-looking statements to reflect subsequent events or circumstances, except as otherwise required by law. Investor Contact:Ashley R. RobinsonLifeSci Advisors, LLC+1 617-430-7577arr@lifesciadvisors.com Media Contact:Darren Opland, Ph.D.LifeSci Communications+1 646-627-8387darren@lifescicomms.com