BeyondSpring’s Plinabulin Stimulates Both the Adaptive & Innate Immune System 

BeyondSpring Inc. recently announced that new clinical data on the company’s first-in-class, late-stage asset, Plinabulin, shows its ability to potently stimulate the innate immune system. Previously, the company reported that Plinabulin stimulates the adaptive immune system, through enhancing Dendritic Cell-dependent T-Cell proliferation (Mita, ASCO-SITC 2017). Dr. Ramon Mohanlal, BeyondSpring’s Chief Medical Officer and Executive Vice President, Research and Development, presented the new clinical evidence as a poster at this year’s ASCO-SITC Clinical Immuno-Oncology Symposium in Orlando, Fla.

Plinabulin can activate the body’s innate immune response by increasing plasma levels of both neutrophil count and the immune-modulatory protein haptoglobin.  In the company’s Phase 2 106 Study in Breast Cancer patients receiving TAC (taxotere, doxorubicin, cyclophosphamide) chemotherapy, Plinabulin was administered as monotherapy at 10 (n=15), 20 (n=15), and 30 (n=12) mg/m2 on Day One after TAC use. Haptoglobin and Absolute Neutrophil Number (ANC) profiles were obtained from blood draws taken before the first dose and almost daily, post-dose through Day 15 in the first cycle.  The data concluded:

-A single Plinabulin dose increased plasma haptoglobin levels within three days (p<0.03), and ANC levels within just one day (p<0.001).

-The mean haptoglobin (p<0.0005) and ANC (p<0.001) levels over 15 days in the first cycle increased approximately two-fold versus baseline levels.

-Haptoglobin levels remained increased for more than three weeks, and ANC levels for approximately one week following just a single dose of Plinabulin.

“This new clinical finding that Plinabulin induces a long-lasting increase in plasma haptoglobin levels is fascinating, considering haptoglobin’s potent ability to activate the innate immune system,” said Dr. Mohanlal. “This data, coupled with our previous observation that Plinabulin increases Neutrophil counts, another member of the innate immune system, we now have multiple lines of clinical evidence to prove that Plinabulin is a potent stimulator of the innate immune systems. The dual ability to stimulate both the adaptive and innate immune system by Plinabulin is very valuable in its use in the prevention of Chemotherapy Induced Neutropenia (CIN) and treatment of cancer.  This not only supports Plinabulin’s current Phase 3 studies in NSCLC and in CIN, but also positions Plinabulin as a preferred agent to be combined with IO therapies such as PD1/PD-L1 inhibitors. Therefore, we have initiated a broad program combining Plinabulin with checkpoint inhibitors with or without radiotherapy or chemotherapy, in collaboration with prominent academic centers and large pharma.”

BeyondSpring is a global, clinical-stage biopharmaceutical company focused on the development of innovative immuno-oncology cancer therapies. BeyondSpring’s lead asset, first-in-class agent Plinabulin as an immune and stem cell modulator, is in a Phase 3 global clinical trial as a direct anticancer agent in the treatment of non-small cell lung cancer (NSCLC) and two Phase 3 clinical programs in the prevention of chemotherapy-induced neutropenia (CIN). BeyondSpring has strong R&D capabilities with a robust pipeline in addition to Plinabulin, including three immuno-oncology assets and a drug discovery platform using the ubiquitination degradation pathway. The company also has a seasoned management team with many years of experience bringing drugs to the global market.

Plinabulin, BeyondSpring’s lead asset, is a differentiated immune and stem cell modulator. Plinabulin is currently in late-stage clinical development to increase overall survival in cancer patients, as well as to alleviate chemotherapy-induced neutropenia (CIN). The durable anticancer benefits of Plinabulin have been associated with its effect as a potent antigen-presenting cell (APC) inducer (through dendritic cell maturation) and T-cell activation. Plinabulin’s CIN data highlights the ability to boost the number of hematopoietic stem/progenitor cells (HSPCs), or lineage-/cKit+/Sca1+ (LSK) cells in mice. Effects on HSPCs could explain the ability of Plinabulin to not only treat CIN but also to reduce chemotherapy-induced thrombocytopenia and increase circulating CD34+ cells in patients.