BeyondSpring Pharmaceuticals’ Data Indicating Plinabulin Enhances Immune Response Provides Basis for Planned Phase I/II Combination Trial in NSCLC

Expanding Plinabulin Immuno-oncology Focus in Combination With PD-1 Inhibitor

New York, New York, UNITED STATES

NEW YORK, Feb. 08, 2016 (GLOBE NEWSWIRE) -- BeyondSpring Pharmaceuticals Inc., a clinical stage biopharmaceutical company focused on the development of innovative cancer therapies including a Phase III immuno-oncology compound and a strong pipeline in collaboration with Fred Hutchinson Cancer Research Center, today announced data from preclinical studies indicating that the Company’s lead oncology asset, Plinabulin, has demonstrated synergistic effect with PD-1 antibody and PD-1 + CTLA-4 antibodies, and exhibits a broad spectrum of immune-enhancing effects that are complimentary to PD-1 inhibitors. These results provide the basis for initiating a phase I/II clinical trial of Plinabulin with Nivolumab in metastatic non-small cell lung cancer (NSCLC), which is planned for the first half of 2016.

In an in vivo immune competent tumor mouse model, intraperitoneal injection of Plinabulin dosed at 7.5 mg/kg biweekly significantly enhanced the therapeutic effect of combined PD-1/CTLA-4 inhibition on tumor volume.  In terms of tumor volume reduction at necropsy, the combination of plinabulin + PD-1 antibody was significantly more effective than PD-1 antibody alone (p=0.04).

Results were presented by Chief Scientific Officer G. Kenneth Lloyd, Ph.D. during a poster presentation “Evidence for an Immune-Mediated Mechanism of Action” (Abstract #A07) at The Function of Tumor Microenvironment in Cancer Progression, which was hosted by the American Association for Cancer Research (AACR) and held in San Diego in January 2016. Data from the study indicate Plinabulin exhibits a broad spectrum of immune-enhancing effect: by increasing dendritic cell maturation as evidenced by elevated levels of specific proteins involved in generating an immune response (CD40, MHCII, CD80 and CD86) and increasing the release of pro-inflammatory cytokines (such as IL-1beta, IL-6 and IL12p40).  In addition, Plinabulin significantly down-regulates Treg (immune suppressive T cells), and macrophages.

Through these studies, Plinabulin has explicitly demonstrated its ability to enhance immune responses relevant to cancer treatment, thereby providing the basis for clinical evaluation co-administered with immuno-oncology therapy.  BeyondSpring plans to initiate a clinical trial in patients with NSCLC to evaluate the effects of Plinabulin in combination with the PD-1 inhibitor, nivolumab (marketed as Opdivo®).

Dr. Lloyd commented, “Evidence from this study indicates compounds that block tubulin polymerization, such as Plinabulin, but not microtubule stabilization – such as docetaxel – exert immune-enhancing effects through dendritic cell maturation and enhanced tumor antigen specific T-cell activation. We are excited to see that Plinabulin was shown to act synergistically with immune checkpoint inhibitors.”

Dr. Ramon Monhanlal, M.D., Ph.D., Chief Medical Officer of BeyondSpring commented, “The immune effect of plinabulin has shown to be complimentary to those exhibited by PD-1 inhibitors.  Together with its vascular disruptive effects, Plinabulin’s immune enhancing effects provide the rationale for us to initiate our immuno-oncology program evaluating the combination of Plinabulin and PD-1 inhibitors.” 

Dr. Lan Huang, Ph.D., co-founder and Chief Executive Officer of BeyondSpring, added, “Plinabulin has been shown in previous clinical studies to exert durable response which is indicative of an immune mechanism in a 163-patient NSCLC phase 2 study in the US and international countries.  These latest mechanism data further confirm the viability of Plinabulin to treat multiple cancer types as an IO agent. The planned Phase I/II combination study in NSCLC at UCSD and the University of Washington, in collaboration with Fred Hutchinson Cancer Research Center and other US clinical centers, is a starting point for BeyondSpring to expanding our focus in the IO field.”

About Plinabulin

BeyondSpring’s lead therapeutic candidate, Plinabulin, has begun a Phase III study to treat non-small-cell lung carcinoma (“NSCLC”). This 550-patient clinical trial is being conducted in the United States, China, and Australia.  Evaluation and enrollment of patients in the U.S. has commenced, with additional sites to be added.  The company recently announced that the China Food and Drug Administration (“CFDA”) has given a CTA (Clinical Trial Authorization) for the initiation of the China arm of the study.

Plinabulin has been evaluated in over 140 patients in the U.S. and select international locations.  It has demonstrated promising anti-cancer activity in addition to a favorable safety profile. Plinabulin works via multiple mechanisms of action to alter the tumor microenvironment such as: 1) acting as an immuno-oncology agent to induce dendritic cell maturation and antigen-specific T cell activation; 2) obliterating existing tumor vasculature by inhibiting tubulin polymerization, and 3) activating the JNK pathway to induce tumor cell apoptosis. Plinabulin may be particularly effective against large tumors because of their more abundant tumor vasculature and greater tumor antigen. BeyondSpring is investigating additional clinical programs for Plinabulin in combination with PD-1/PD-L1 inhibitors and for other indications.

About BeyondSpring Pharmaceuticals

BeyondSpring Pharmaceuticals is a clinical stage biopharmaceutical company focused on the development of innovative cancer therapies. BeyondSpring is focused on the advancement and commercialization of Plinabulin, a novel, Phase III cancer therapeutic initially targeting non-small-cell lung cancer.

Operationally, BeyondSpring utilizes a unique U.S.-China co-development platform to optimize clinical development speed while reducing costs. The Company has significant experience interacting with the FDA and CFDA. Thus, patient recruitment and clinical trials can be run simultaneously in both geographies, which offers the potential to substantially lower the cost of drug discovery/development and increase the speed of advancing novel therapies to clinical trials and, ultimately, to the market.

The Company has additional next-generation immuno-oncology assets, as well as a technology platform for targeted drugs and at least 6 new development compounds per year through a recently-established 5 year research collaboration with the Fred Hutchinson Cancer Research Center.

Led by an expert management team consisting of pharmaceutical industry veterans from the U.S. and China, the Company is well positioned to further advance lead product candidate, Plinabulin, and its other programs. For more information, visit