BeyondSpring Pharmaceuticals Announces New Clinical Data Confirming Plinabulin’s Fast Onset Mechanism of Action in the Prevention of Chemotherapy-Induced Neutropenia at the 63rd ASH Annual Meeting and Exposition

Rhea-AI Summary

BeyondSpring Pharmaceuticals has released new data at the ASH Annual Meeting demonstrating that plinabulin rapidly reverses chemotherapy-induced neutropenia (CIN) and leukopenia within 24 hours. This effect is attributed to its mechanism of protecting granulocyte-monocyte-progenitor stem cells, with statistical significance marked at p<0.0001. The findings affirm the positive results from the Phase 3 PROTECTIVE-2 study, supporting plinabulin's role in enhancing CIN prevention strategies and potentially improving patient outcomes during chemotherapy.

Positive

• Plinabulin shows rapid (within 24 hours) efficacy in reversing chemotherapy-induced neutropenia and leukopenia.
• Mechanism of action supports protection of progenitor stem cells, crucial for effective CIN management.
• Data reinforces prior positive Phase 3 outcomes from the PROTECTIVE-2 study.

Negative

• None.

• Adding plinabulin to a myelosuppressive chemotherapy regimen rapidly reversed (within 24 hours) chemotherapy-induced neutropenia and leukopenia in the PROTECTIVE-1 and -2 clinical studies, suggesting protection of the granulocyte-monocyte-progenitor stem cells as plinabulin’s mechanism of action for the prevention of chemotherapy-induced neutropenia (CIN), at a level of p<0.0001 with the CIN dose of plinabulin
  
• The data were presented in a poster at ASH on Sunday, December 12, 2021

NEW YORK, Dec. 15, 2021 (GLOBE NEWSWIRE) -- BeyondSpring Pharmaceuticals (the “Company” or “BeyondSpring”) (NASDAQ: BYSI), a global pharmaceutical company focused on the development of cancer therapeutics, today announced new data highlighting the mechanism of action of plinabulin in the prevention of chemotherapy-induced neutropenia (CIN) at the 63^rd American Society of Hematology (ASH) Annual Meeting and Exposition, held virtually and in person in Atlanta, Georgia from December 11-14, 2021. The data demonstrate that adding plinabulin to a myelosuppressive regimen rapidly reversed (within 24 hours) neutropenia and leukopenia in the PROTECTIVE-1 and -2 clinical studies by protecting progenitor stem cells in the bone marrow.

“This clinical data provides evidence confirming the hypothesized progenitor stem cell protective mechanism of action for plinabulin, which further validates the positive Phase 3 data from the PROTECTIVE-2 clinical program. These data also build upon the rapid effect seen in clinical trials to date and support the opportunity for enhanced CIN prevention care with plinabulin,” said Dr. Douglas Blayney, professor of medicine at Stanford University Medical School and global principal investigator for the CIN studies. “These data provide a strong rationale for combining plinabulin with pegfilgrastim, since the latter has a mechanism of action exerting CIN prevention in week 2 of the chemotherapy cycle while plinabulin shows a week 1 benefit. This early CIN benefit is critically important because these white blood cells are the body’s main source of defense against infection. If a cancer patient gets an infection due to CIN, it may affect their ability to finish chemotherapy for cancer treatment.” 

Dr. Ramon Mohanlal, executive vice president of research and development and chief medical officer at BeyondSpring Pharmaceuticals, added, “This presentation at ASH provides mechanistic support for the observed benefit of plinabulin in the prevention of CIN, a condition that still has unmet medical need, despite the availability of the standard of care CIN prevention drug, G-CSF. In addition, the rapid onset of action is critical since week 1 of each chemotherapy cycle is when more than 75% of CIN cases occur, even with G-CSF. Investigating the nuances of how and when plinabulin works is a continuous part of our work in understanding this multifaceted therapy. We look forward to sharing more of these insights with the oncology community in future studies.”

This poster was presented on Sunday, December 12, 2021 and is available on the ASH website.

Poster Title: Plinabulin Rapidly (within 24 Hours) Reverses Myelosuppression Induced by Chemotherapy
Abstract Number: 2056
Key Findings:

• This new data analysis from the PROTECTIVE-1 and 2 studies aimed to further evaluate plinabulin’s fast onset mechanism of action (MoA) and potential progenitor stem cell involvement in plinabulin’s fast onset MoA.
• The comparison was made between cancer patients receiving plinabulin 40 mg (n=228) or not receiving plinabulin (n=172), and with all patients receiving myelosuppressive chemotherapy (docetaxel with or without doxorubicin and cyclophosphamide). Plinabulin 40 mg was given 30 minutes after chemotherapy.
• Plinabulin rapidly (within 24 hours) reversed chemo-induced myelosuppression in both the PROTECTIVE-1 and 2 human studies. Plinabulin-mediated increases in cell numbers are dose-dependent and correlated among cells of the myeloid, lymphoid and erythroid lineages.
  • Neutrophils (p<0.0001; increase by >3x10E9/L with plinabulin and decrease by >0.5x10E9/L without plinabulin)
  • Monocytes (p=0.0023)
  • Eosinophils (p=0.0775)
  • Basophils (p<0.0001)
• The data suggest that plinabulin targets granulocyte-monocyte-progenitor (GMP) stem cells (N, M, B and E progenitor) as well as progenitor cells further upstream in the hematopoietic lineage.

About Plinabulin 
Plinabulin, BeyondSpring’s lead asset, is a selective immunomodulating microtubule-binding agent (SIMBA), which is a potent antigen presenting cell (APC) inducer. It is a novel, intravenous infused, patent-protected asset for CIN prevention and a Phase 3 anti-cancer candidate for non-small cell lung cancer (NSCLC) with recently released positive topline data. Plinabulin triggers the release of the immune defense protein, GEF-H1, which leads to two distinct effects: first is a durable anticancer 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 early-onset of action in CIN prevention after chemotherapy by boosting the number of hematopoietic stem/progenitor cells (HSPCs). Plinabulin received Breakthrough Therapy designation from both U.S. and China FDA for the CIN prevention indication. As a “pipeline in a drug,” plinabulin is being broadly studied in combination with various immuno-oncology agents that could boost the effects of the PD-1/PD-L1 antibodies and re-sensitize PD-1/PD-L1 antibody-resistant patients. 

About BeyondSpring Pharmaceuticals 
Headquartered in New York City, BeyondSpring is a 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, a selective immunomodulating microtubule-binding agent (SIMBA), is being developed as a “pipeline in a drug” in various cancer indications as a direct anti-cancer agent and to prevent chemotherapy-induced neutropenia (CIN). In the DUBLIN-3 study, a global, randomized, active controlled Phase 3 study, the plinabulin and docetaxel combination has met the primary endpoint of extending overall survival compared to docetaxel alone, in 2^nd/3^rd line NSCLC (EGFR wild type). Additionally, it is being broadly studied in combination with various immuno-oncology regimens that could boost the effects of PD-1 / PD-L1 antibodies in seven different cancers. In addition to plinabulin, BeyondSpring’s extensive pipeline includes three pre-clinical 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 our 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. Robinson 
LifeSci Advisors, LLC 
+1 617-430-7577 
arr@lifesciadvisors.com 

Media Contact: 
Darren Opland, Ph.D. 
LifeSci Communications 
+1 646-627-8387 
darren@lifescicomms.com  

FAQ

What are the key findings about plinabulin from the ASH Annual Meeting?

Plinabulin rapidly reverses chemotherapy-induced neutropenia and leukopenia within 24 hours, demonstrating a protective mechanism on stem cells.

How does plinabulin compare to existing CIN prevention drugs?

Unlike standard CIN drugs like G-CSF, plinabulin provides early benefits, particularly in the first week of chemotherapy.

What is the significance of the statistical data presented for plinabulin?

The results showed significant improvement with p<0.0001, indicating strong efficacy in preventing CIN.

What are the clinical implications of plinabulin's rapid onset of action?

The rapid action is critical as it might prevent infections that can interfere with chemotherapy treatments.