- Plinabulin rapidly (within 24 hours) mitigates chemotherapy-induced myelosuppression by protecting bone marrow granulocyte-monocyte progenitor (GMP) stem cells
NEW YORK, September 13, 2022 – 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 #: 1588P
Presenter: 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
|Pre-dose C1D1 control
|p-value||24 hours post-plinabulin
|24 hours post-control
|Promyelocytes||0 (0)||0 (0)||NA||2 (0.7)||0 (0)||0.25|
|Myelocytes||1 (0.4)||1 (0.5)||0.8||23 (7.7)||0 (0)||<0.0001|
|Metamyelocytes||1 (0.4)||1 (0.5)||0.8||20 (6.7)||0 (0)||0.0002|
|Bands||11 (3.7)||9 (4.5)||0.6||21 (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.”
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).
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 Statements
This 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.
Ashley R. Robinson
LifeSci Advisors, LLC
Darren Opland, Ph.D.