Data Presented Shows Plinabulin Mobilizes Bone Marrow CD34+ Progenitor Cells through a Mechanism of Action Independent from G-CSFs and CXCR4
NEW YORK, June 30, 2020 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (the “Company” or “BeyondSpring”) (NASDAQ:BYSI), a global biopharmaceutical company focused on the development of innovative immuno-oncology cancer therapies, today announced that the Company presented clinical data on BeyondSpring’s first-in-class, late-stage asset, Plinabulin, showing potent CD34+ progenitor cell mobilization from bone marrow, which has broad applications for stem cell-based therapies, gene therapy and regenerative medicine. These findings potentially add another indication to Plinabulin, which is known as a “pipeline in a drug.” Dr. Ramon Mohanlal, BeyondSpring’s Chief Medical Officer and Executive Vice President, Research and Development, presented this new data as a poster at this year’s ISSCR Annual Meeting.
Current approved agents for CD34+ progenitor cell mobilization, such as G-CSFs or Plerixafor (CXCR4-antagonist), have many limitations. While G-CSFs are highly effective in preventing chemotherapy-induced neutropenia (CIN), they come with severe side effects, such as bone pain and thrombocytopenia. To add, multiple doses of short-acting G-CSFs (up to six or seven) are often needed for the therapy to be effective. Plerixafor is also given by daily injections for four to five days and is a very expensive process and not as effective for CD34+ cells (American Health and Drug Benefits, 2012).
Additionally, G-CSFs are contra-indicated in Sickle Cell Disorder (SCD) patients undergoing gene therapy. This results in high rates of adverse events requiring hospitalization, including vaso-occlusive crises, multi-organ failure and even death (Chien, Haematologica 2018). Lastly, when side effects such as bone pain, leukocytosis (high white blood cell count) and / or myalgia (muscle pain) occur, a G-CSF dose is often reduced to 50 percent, which is less effective for CD34+ cell mobilization.
Plinabulin is a novel and potent agent for the prevention of CIN and does not cause bone pain or thrombocytopenia. Plinabulin is given as a single fixed dose (40mg) - as a 30-minute intravenous infusion - and has a mechanism of action independent from G-CSF of CXCR4.
In BeyondSpring’s PROTECTIVE-2 Phase 2 study, the team evaluated the effects of CD34+ cell mobilization through combining Plinabulin with the full dose of Pegfilgrastim (Peg) at 6mg and at lower doses of 3mg and 1.5mg in breast cancer patients receiving taxotere, doxorubicin and cyclophosphamide (TAC).
- The data shows that combining Plinabulin with a low dose of Pegfilgrastim produces statistically significant CD34+ cell counts (p<0.03) and increases to values that are comparable to, or numerically higher than, the full dose of Pegfilgrastim alone under severe myelosuppressive conditions.
In BeyondSpring’s PROTECTIVE-1 Phase 2 study, the Company previously reported that lung cancer patients receiving docetaxel who received a single dose of Plinabulin saw an increase of CD34+ counts to clinically and statistically significant (p<0.001) levels under myelosuppressive conditions (Blayney, ASH 2018).
The above data presentation is available on the “Posters” page of BeyondSpring’s website. Please click here for more information.
“Plinabulin’s mechanism of action for CD34+ cell mobilization, which is independent from G-CSFs or CXCR4, offers an important alternative to patients who do not adequately respond to these agents, including patients where G-CSFs are contra-indicated,” said Dr. Mohanlal. “Stem cell-based applications, such as gene therapy, is bound to become the standard of care for SCD, for which Plinabulin is well-positioned for CD34+ cell mobilization, given that G-CSFs are contra-indicated for SCD patients. With more than 100,000 SCD patients in the U.S. alone, this represents a near-term opportunity for Plinabulin, along with other CD34+ progenitor cell applications.”