Press Release

BeyondSpring Presents Promising Data for Lead Asset Plinabulin at 2018 ASCO-SITC Clinical Immuno-Oncology Symposium

Plinabulin and Neulasta have Very Similar Grade 4 Neutropenia Incidence and Duration of Severe Neutropenia (DSN) in the Phase 2 Portion of Phase 2/3 Trial Study 105 with Docetaxel-Induced Neutropenia

Initial Phase 1 Results in Investigator-Initiated Trials Highlight Plinabulin’s Safety in Combination with Immuno-Oncology Agent Nivolumab

NEW YORK, Jan. 26, 2018 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (NASDAQ:BYSI), a global clinical-stage biopharmaceutical company focused on the development of innovative immuno-oncology cancer therapies, announced that the Company presented data from several studies of its lead asset, Plinabulin, at the 2018 ASCO-SITC Clinical Immuno-Oncology Symposium. The Phase 2 portion of its global Phase 2/3 clinical trial (Study 105) for the prevention of docetaxel chemotherapy-induced neutropenia (CIN) demonstrated that the duration of severe neutropenia (DSN) data for Plinabulin is very similar to the DSN of Neulasta. Incidence of Grade 4 neutropenia was the same for Neulasta as for 20mg/m2 Plinabulin. The primary objective of the Phase 2 portion, which was to identify the recommended Phase 3 dose (RP3D), has been met, and the Company has begun preparations to move into the Phase 3 portion of Study 105.

Study 105: Plinabulin-Docetaxel CIN Treatment

Patient enrollment in the Phase 2 portion has been completed. A total of N=55 patients with advanced or metastatic NSCLC were enrolled. Patients were randomly assigned to the following arms (with the respective sample sizes):

Arm 1: Docetaxel (Day 1, 75 mg/m2) + pegfilgrastim (Day 2, 6 mg) (N=14)
Arm 2: Docetaxel (Day 1, 75 mg/m2) + Plinabulin (Day 1, 20 mg/m2) (N=14)
Arm 3: Docetaxel (Day 1, 75 mg/m2) + Plinabulin (Day 1, 10 mg/m2) (N=14)
Arm 4: Docetaxel (Day 1, 75 mg/m2) + Plinabulin (Day 1, 5 mg/m2) (N=13)

The topline data from the Phase 2 portion of Study 105 is summarized below. For grade 4 neutropenia and DSN, there is an apparent dose-response, favoring the 20 mg/m2 Plinabulin dose.

Neutropenia Neulasta
6 mg
N=14
Plinabulin
5 mg/m2
N=14
Plinabulin
10 mg/m2
N=14
Plinabulin
20 mg/m2
N=13
Grade 4 Incidence % 14 % 23 % 21 % 15 %
DSN (Days) 0.14   0.46   0.43   0.38  

“This data is extremely promising for BeyondSpring, because this is the first head-to-head comparison with Neulasta, demonstrating very similar Grade 4 Neutropenia incidence and DSN for Plinabulin and Neulasta,” said Dr. Douglas Blayney, principal investigator for both of BeyondSpring’s ongoing registrational neutropenia trials. “This data identified an apparent dose response and the RP3D with Plinabulin that will be moved to Phase 3 testing against the current standard of care, Neulasta, in Taxotere-treated cancers. We’re very encouraged to see strong interest within the medical community participating in this trial, resulting in a faster-than-expected enrollment. We look forward to confirmation of this data in the Phase 3 portion of Study 105, as well as to see the Phase 2 data of Study 106 in mid-2018, comparing Plinabulin with Neulasta in CIN induced by Taxotere/Adriamycin/Cyclophosphamide (TAC) chemotherapy for breast cancer.”

Plinabulin is a non-G-CSF agent that prevents CIN through a mechanism different from G-CSF by sustaining neutrophil levels within the normal range via reversal of the block of neutrophil formation in the bone marrow induced by docetaxel. Plinabulin had been shown to prevent neutropenia caused by a number of chemotherapeutics with different anti-tumor mechanisms in preclinical studies. BeyondSpring believes that Plinabulin offers a differentiated alternative to G-CSF, has demonstrated anti-cancer activity in NSCLC patients, is administered 30 minutes after chemotherapy and does not cause bone pain. In contrast, G-CSF is given 24 hours after chemotherapy and causes bone pain in many patients. We conclude that a single dose of 20 mg/m2, 30 minutes after docetaxel, is the recommended Phase 3 dose for Study 105.

Triple Immuno-Oncology Strategy

In addition, BeyondSpring announced its plans to initiate a broad program with triple combinations in immuno-oncology. Two types of triple combinations will be initiated: first, PD1-inibitor/CTLA4-inhibitor/Plinabulin and, second, PD1-inhibitor/chemotherapy/Plinabulin. BeyondSpring presented initial Phase 1 safety data from a study of Plinabulin in combination with Nivolumab for the treatment of NSCLC, which was conducted by collaborators at the Fred Hutchinson Cancer Research Center and University of California, San Diego. The Company’s poster also highlighted Plinabulin’s immune-enhancing effects when combined with docetaxel, which shows prolongation of the duration of response (DoR), an indication of an immune-enhancing mechanism, compared to docetaxel alone.

Plinabulin appears to be a PDE4-inhibitor at clinically relevant doses. PDE4-inhibitors are potent anti-inflammatory agents that are approved to date to treat inflammatory disorders like eczema, psoriasis and chronic obstructive pulmonary disease (COPD), with resemblance to immune-related adverse events (IR-AEs) as observed with checkpoint inhibitors.

In the two Phase 1 studies with NSCLC patients, a total of 10 patients have been enrolled to date and received Nivolumab (240 mg or 3 mg/kg) in combination with Plinabulin at 13.5 mg/m2 (N=3), 20 mg/m2 (N=5) or ~30 mg/m2 (N=2). The data shows that no grade 3/4 IR-AEs were observed. Two patients had developed either grade 1 or 2 IR-AEs without the need for steroid treatment.

The Company also presents non-clinical and preliminary clinical data to demonstrate Plinabulin’s immune-enhancing effects, resulting in improved anticancer efficacy compared to checkpoint inhibitors or chemotherapy alone. Plinabulin exerts immune-enhancing effects through the activation of dendritic cells and the antigen-specific proliferation of T-cells.

Plinabulin in combination with docetaxel significantly (P<0.05) prolonged the DoR in NSCLC patients, compared to docetaxel alone in a Phase 2 study (Study 101).

  Plinabulin + Docetaxel Docetaxel Alone
Duration of Response 12.7 Months 1.0 Months

In the immune-competent MC38 animal model, the triple combination of Plinabulin and PD-1 and CTLA-4 antibodies showed around four times more tumor inhibition compared to PD-1 antibodies alone, while the combination of Plinabulin and PD-1 antibodies showed around two times more tumor inhibition compared to PD-1 antibodies alone.

“Preliminary clinical data suggests that the addition of Plinabulin to checkpoint inhibitor therapy would prevent IR-AEs,” added Dr. Ramon Mohanlal, EVP and Chief Medical Officer at BeyondSpring. “Plinabulin is uniquely positioned as an agent with immune-enhancing effects, in combination with anti-inflammatory effects, to be combined with the PD1 inhibitor/CTLA4-inhibitor, which is known to cause IR-AEs in a majority of patients. The addition of Plinabulin to PD1-inhibitor/CTLA4-inhibitor is expected to not only reduce IR-AEs but also increase overall anticancer efficacy. With the triple IO combination with PD1-inhibitor/chemotherapy/Plinabulin, the addition of Plinabulin is expected to prevent not only IR-AEs but also CIN, while adding to overall efficacy. Phase 1/2 IIT studies with either of the triple combinations with Plinabulin will be initiated shortly.”

“We are highly encouraged with the steady flow of data that is being generated with Plinabulin, which provides strong justification for advancing Plinabulin as a platform drug toward commercialization in multiple indications,” concluded Dr. Lan Huang, BeyondSpring’s CEO. “With the CIN indication, we have a near-to-market oncology opportunity in a large global market. We expect the triple IO combinations, which are expected to materialize thereafter, to solidify our position as a key player in the oncology space.”

As previously communicated, BeyondSpring management will host a conference call with the investment community to review these important data on Jan. 29, 2018, at 8:30 a.m. ET. The conference call will feature remarks by Dr. Huang, Dr. Mohanlal and Dr. Blayney, Board Member of the NCCN Guidelines for neutropenia management, who served as an investigator in clinical trials for Neupogen and Neulasta and is the principal investigator for both of BeyondSpring’s ongoing registrational neutropenia trials. The dial-in numbers for the call are +1.877.451.6152 (U.S. toll free) or +1.201.389.0879 (international). Please ask the operator to join the BeyondSpring call.

A live webcast of the call will also be available online, which can be accessed through the Investor Relations section of BeyondSpring’s website: http://ir.beyondspringpharma.com. Please allow extra time prior to the call to visit the site and download any necessary software to listen to the live broadcast.

For interested individuals who are unable to join the conference call, a replay of the call will be available through Feb. 12, 2018, at +1.844.512.2921 (U.S. toll free) or +1.412.317.6671 (international). Participants must use the following code to access the replay of the call: 13675621. A replay of the webcast will remain available on http://ir.beyondspringpharma.com for 30 days following the call.

About BeyondSpring
BeyondSpring is a global clinical stage biopharmaceutical company developing innovative immuno-oncology cancer therapies with a robust pipeline from internal development and from collaboration with University of Washington in de novo drug discovery using ubiquitination platform. BeyondSpring’s lead asset, Plinabulin, is in a Phase 3 clinical trial as a direct anticancer agent in non-small cell lung cancer (Study 103) and two Phase 2/3 clinical programs in the prevention of chemotherapy-induced neutropenia (CIN) – Studies 105 and 106. BeyondSpring has a seasoned management team with many years of experience bringing drugs to market.

About Plinabulin
Studies on Plinabulin's mechanism of action indicate that Plinabulin activates GEF-H1, a guanine nucleotide exchange factor. GEF-H1 activates downstream transduction pathways leading to the activation of the protein c-Jun. Activated c-Jun enters the nucleus of dendritic cells to upregulate immune-related genes, which contributes to the up-regulation of a series of genes leading to dendritic cell maturation, T-cell activation and other effects that prevent neutropenia. Plinabulin is given as a single IV infusion in each cycle, 30 minutes to 1 hour after completion of the chemotherapy, offering same day dosing, whereas G-CSF is given 24 hours after chemotherapy. In addition, the use of Plinabulin is not associated with bone pain, which is a frequent side effect with G-CSF.

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, the anticipated amount needed to finance the company's future operations, unexpected results of clinical trials, delays or denial in regulatory approval process, our expectations regarding the potential safety, efficacy or clinical utility of our product candidates, or additional competition in the market. The 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 Relations:
Steve Silver / Jeffrey Goldberger
KCSA Strategic Communications
212-682-6300
ssilver@kcsa.com / jgoldberger@kcsa.com

Media Relations:
Caitlin Kasunich / Amy Singh
KCSA Strategic Communications
212.896.1241 / 212.896.1207
ckasunich@kcsa.com / asingh@kcsa.com

BeyondSpring, Inc.