Preparing to Submit NDA in China for Chemotherapy-Induced Neutropenia (“CIN”) in Q1 2020
Plinabulin’s Anti-Cancer and CIN Prevention Mechanism Published in Peer Reviewed Journals
NEW YORK, Dec. 18, 2019 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (the “Company” or “BeyondSpring”) (NASDAQ: BYSI), a global biopharmaceutical company focused on the development of innovative cancer therapies, today provided an update on the Company’s operations and announced its financial results for the three months ended September 30, 2019.
“We are pleased with the progress we are seeing in our clinical programs surrounding our lead compound, Plinabulin, for the treatment of non-small cell lung cancer (NSCLC) and CIN,” said Dr. Lan Huang, BeyondSpring’s Co-Founder, Chairman and Chief Executive Officer. “Our goal from day one has been to develop transforming treatments for cancer patients. Between the enrollment of the first patient in our global Phase 3 Study 106, the publication of Plinabulin’s immune mechanism as a potent Antigen Presenting Cell (APC) inducer in three peer-review journals and continual positive data being presented at medical meetings world-wide, we remain on track to address large unmet medical needs among these cancer patients.”
“The combination of our clinical experience – over 900 patients enrolled globally – and the deep insight into Plinabulin’s immune mechanism – a potent APC inducer – lead us to believe Plinabulin has potential to be a ’pipeline in a drug’. Our life cycle plan for Plinabulin begins with the foundational indications in NSCLC and CIN. From here we expect to expand into a broader chemotherapy combination footprint, and eventually we expect to transform Plinabulin’s potential in combination with checkpoint inhibitors and radiation or chemotherapy. This triple therapy combination could be a powerful treatment in multiple cancer types with significant market opportunities,” added Dr. Huang. “We anticipate filing NDAs for Plinabulin in the U.S. and China for both NSCLC and CIN over the next 18 months. The success of our recent round of financing ensures that we will have the necessary resources to achieve the clinical milestones moving forward.”
Recent Operational Highlights
Novel Study Design of Plinabulin in NSCLC Phase 3
In October 2019, BeyondSpring announced that its abstract, titled, “DUBLIN-3, a Stage IIIb / IV NSCLC Phase 3 Trial Comparing the Plinabulin / Docetaxel Combination with Docetaxel Alone,” was presented at this year’s European Society for Medical Oncology (ESMO) Congress. The abstract highlighted the study’s unique design, which positively addressed the challenges associated with trial failure risk in NSCLC studies.
In November 2019, BeyondSpring presented a poster at the Society for Immunotherapy of Cancer (SITC) Annual Meeting, titled, “Validation of a Single-Blinded (Patients Only) Study Design for the Prevention of Premature Patient Consent Withdrawal in the Immuno-Oncology Trial DUBLIN-3.” This abstract explained that cancer patients generally prefer immunotherapy over chemotherapy, which can lead to premature withdrawal of their consent to participate in a clinical trial if they are allocated to the chemotherapy comparator arm, and can negatively impact the study’s outcome. Specifically, the DUBLIN-3 trial was a single-blinded study, while the Javelin trial was an open-label study, which led investigators to their conclusion.
Plinabulin’s Superior Profile in CIN Prevention
In September 2019, BeyondSpring announced that an abstract, titled, “The Effect of Increasing Doses of Pegfilgrastim on Thrombocytopenia in Breast Cancer Patients Receiving Taxotere, Doxorubicin, Cyclophsophamide and Plinabulin,” was accepted for presentation at ESMO. The abstract evaluated the effects of pegfilgrastim combined with Plinabulin on absolute neutrophil and platelet counts compared to pegfilgrastim alone. The data showed that the combination appears to have a superior product profile over pegfilgrastim in CIN control, platelet counts and bone pain.
In October 2019, BeyondSpring announced the enrollment of the first patient in its Study 106, a global Phase 3 trial with Plinabulin in combination with G-CSF to prevent CIN. The study is the key platform to confirm this finding and bring improved care to patients.
Most recently at the American Society of Hematology’s (ASH) annual meeting, BeyondSpring presented two e-publications on Study 105 and a poster on Study 106, highlighting Plinabulin’s mechanism of action in preventing CIN.
The Study 105 e-publications titled, “Clinical Evidence of Granulocyte-Monocyte Progenitor (GMP) Stem Cell Involvement in Plinabulin’s Mechanism of Action (MoA) for the Prevention of Docetaxel (Doc) Chemotherapy (Chemo)-Induced Neutropenia (CIN),” and “Clinical Evidence Against the Continuum of Low-Primed Uncommitted Hematopoietic and Progenitor Cells (CLOUD-HSPC) Concept for Hematopoiesis,” highlight Plinabulin’s ability to protect hematopoietic stem cells, which differentiates into neutrophils and other white blood cells.
The Study 106 poster titled, “A Randomized Phase 3 Clinical Trial of the Combination of Plinabulin (Plin) + Pegfilgrastim (Peg) versus (vs) Peg Alone for TAC (docetaxel, doxorubicin, cyclophosphamide) Induced Neutropenia (CIN),” provides rationale for the addition of Plinabulin to pegfilgrastim (Neulasta) due to their differing mechanisms of action (MoA) for the prevention against CIN.
Plinabulin’s Anti-cancer Immune Mechanism and CIN Prevention Mechanism Published in Peer-Reviewed Journals
In October 2019, prestigious Cell publications, Chem and Cell Reports, published novel findings focusing on the mechanism of Plinabulin to mature dendritic cells, which leads to T-cell activation.
The Chem article, titled, “Structure, Thermodynamics and Kinetics of Plinabulin Binding to Two Tubulin Isotypes,” outlined research utilizing X-ray crystallography and thermodynamic calculations to demonstrate Plinabulin as a new chemical entity with differentiated binding and kinetics compared to other tubulin binding agents, which gives rise to its differentiated superior efficacy and safety profile in the clinic.
In Cell Reports, titled, “GEF-H1 Signaling Upon Microtubule Destabilization Is Required for Dendritic Cell Activation and Specific Anti-tumor Responses,” authors cited Plinabulin’s ability to destabilize microtubule and release the immune defense protein GEF-H1, which is a critical signaling protein for dendritic cell maturation. This leads to the priming of CD8 T-cells. GEF-H1 high immune signature showed better survival in cancer patients, which validated GEF-H1 as a first in class target.
In early December, Cancer Chemotherapy & Pharmacology published an article that examines the mechanism-of-action of Plinabulin and its anti-CIN benefits. The article, titled, “Plinabulin Ameliorates Neutropenia Induced by Multiple Chemotherapies Through a Mechanism Distinct from G‑CSF Therapies,” reports the results of an animal study that support the clinical testing of Plinabulin as a non-G-CSF-based treatment for CIN associated with chemotherapies of different mechanisms. Results also support hematopoietic stem/progenitor cells as a focal point for future mechanism-of-action work aimed at understanding the ability of Plinabulin to reduce the serious side effect of cytotoxic therapy in cancer patients.
Strong Intellectual Property Protection through 2036 Globally
In October 2019, BeyondSpring announced that the U.S. Patent and Trademark Office granted the Company a new patent for methods of treating brain tumors by administering Plinabulin. This underscores the Company’s belief that Plinabulin is a first-in-class clinical pipeline asset. Currently, surgery and radiation are the only approved treatments for brain tumors. Chemotherapy has never been approved to treat metastatic brain tumors.
We now have 75 granted Plinabulin patents in 36 jurisdictions and 17 patents granted in the U.S., including the composition of matter patent, with protection to 2036.
Equity Financing
On October 25, 2019, BeyondSpring priced an underwritten public offering of its ordinary shares. The offering was led by Decheng Capital, with gross proceeds of $25.8 million including the overallotment options, before deducting underwriting discounts, commissions and other offering expenses. The Company expects to use the net proceeds to continue clinical and pre-clinical development in addition to general corporate purposes.
Financial Results for the Three Months Ended September 30, 2019
Research and development (“R&D”) expenses were $7.2 million for the quarter ended September 30, 2019, compared to $14.1 million for the quarter ended September 30, 2018. The $6.9 million decrease was largely attributable to a $3.9 million decrease in expenses incurred by clinical research organizations and other service fees related to clinical trials, a $0.5 million decrease in preclinical trial expenses and a $0.5 million decrease in non-cash share-based compensation.
General and administrative (“G&A”) expenses were $2.5 million for the quarter ended September 30, 2019, compared to $1.5 million for the quarter ended September 30, 2018. The $1.0 million increase was mainly due to the $0.7 million of market research expenses incurred during the quarter ended September 30, 2019.
Net loss attributable to the Company was $9.4 million for the quarter ended September 30, 2019, compared to $14.9 million for the quarter ended September 30, 2018.
As of September 30, 2019, the Company had a cash balance of $24.7 million. With the additional $25.8 million gross proceeds from the recent public offering described above, the Company believes it has sufficient cash to support its clinical trials and submit NDAs in the U.S. and China for Plinabulin for the treatment of NSCLC and CIN, as well as to advance its immuno-oncology pipeline and its ubiquitination protein degradation research platform.
Anticipated Milestones
The following outlines the Company’s anticipated upcoming milestones and projected timelines:
- NDA submission to China’s National Medical Products Administration (NMPA) for Plinabulin for CIN – Q1 2020
- Final data readout for Study 105 Phase 3 for CIN – H1 2020
- Final data readout for Study 106 Phase 3 for CIN – H1 2020
- Final data readout for Study 103 Phase 3 for NSCLC – H2 2020
- NDA submission to China’s NMPA for Plinabulin for NSCLC – H2 2020
- NDA submission to the U.S. Food and Drug Administration (FDA) for Plinabulin for CIN – H2 2020
- NDA submission to the U.S. FDA for Plinabulin for NSCLC – H1 2021
Conference Call and Webcast Information
BeyondSpring’s management will host a conference call and webcast today at 8 a.m. Eastern Time to discuss the financial results and provide a corporate update. The dial-in numbers for the conference call are 1-877-451-6152 (U.S.) or 1-201-389-0879 (international). Please reference conference ID 13697474. A live webcast will be available on BeyondSpring’s website at www.beyondspringpharma.com under “Events & Presentations” in the Investors section. An archived replay of the webcast will be available for 30 days.
About BeyondSpring
BeyondSpring is a global, clinical-stage biopharmaceutical company focused on the development of innovative immuno-oncology cancer therapies. BeyondSpring’s lead asset, Plinabulin, is in two Phase 3 global clinical programs, one as a direct anticancer agent in the treatment of non-small cell lung cancer (NSCLC) and the other 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.
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,” “potential,” “suggest,” “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. Certain of the statements made in this press release are forward-looking, such as those, among others, relating to BeyondSpring’s expectations regarding the completion of the proposed offering. No assurance can be given that the offering discussed above will be consummated, or that the net proceeds of the offering will be used as indicated. Consummation of the offering and the application of the net proceeds of the offering are subject to numerous possible events, factors and conditions, many of which are beyond the control of the Company and not all of which are known to it, including, without limitation, market conditions and those described under the heading “Risk Factors” in the Company's Annual Report on Form 20-F for the year ended December 31, 2018, as updated by those risk factors included in the Company’s subsequent filings under the Securities Exchange Act of 1934, as amended, which can be accessed at the SEC's website at www.sec.gov. 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, its expectations regarding the potential safety, efficacy or clinical utility of its product candidates, or additional competition in the market, and other risk factors referred to in BeyondSpring’s current Form 20-F on file with the SEC. 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.
| BEYONDSPRING INC. | |||||
| AUDITED CONSOLIDATED BALANCE SHEET AS OF DECEMBER 31, 2018 AND | |||||
| UNAUDITED INTERIM CONDENSED CONSOLIDATED BALANCE SHEET AS OF SEPTEMBER 30, 2019 | |||||
| (Amounts in thousands of U.S. Dollars (“$”), except for number of shares and per share data) | |||||
| December 31, | September 30, | ||||
| 2018 | 2019 | ||||
| $ | $ | ||||
| (Unaudited) | |||||
| Assets | |||||
| Current assets: | |||||
| Cash and cash equivalent | 3,889 | 24,678 | |||
| Advances to suppliers | 1,209 | 5,201 | |||
| Due from related parties | 481 | - | |||
| Prepaid expenses and other current assets | 292 | 481 | |||
| Total current assets | 5,871 | 30,241 | |||
| Noncurrent assets : | |||||
| Property and equipment, net | 282 | 217 | |||
| Operating lease right-of-use assets | - | 2,704 | |||
| Other noncurrent asset | 910 | 978 | |||
| Total noncurrent assets | 1,192 | 3,899 | |||
| Total assets | 7,063 | 34,140 | |||
| Liabilities and equity | |||||
| Current liabilities: | |||||
| Accounts payable | 9,586 | 1,948 | |||
| Accrued expenses | 5,495 | 4,790 | |||
| Current portion of operating lease liabilities | - | 542 | |||
| Other current liabilities | 1,364 | 1,089 | |||
| Total current liabilities | 16,445 | 8,369 | |||
| Noncurrent liabilities: | |||||
| Long-term loans | - | 1,399 | |||
| Operating lease liabilities | - | 2,091 | |||
| Total noncurrent liabilities | - | 3,490 | |||
| Total liabilities | 16,445 | 11,859 | |||
| Equity (Deficit): | |||||
| Ordinary shares ($0.0001 par value; 500,000,000 | |||||
| shares authorized; 23,184,612 and 25,964,190 shares | |||||
| issued and outstanding as of December 31, | |||||
| 2018 and September 30, 2019, respectively) | 2 | 3 | |||
| Additional paid-in capital | 170,950 | 223,019 | |||
| Accumulated deficit | (178,760 | ) | (202,772 | ) | |
| Accumulated other comprehensive income | 42 | 225 | |||
| Total BeyondSpring Inc.’s shareholder’s (deficit) equity | (7,766 | ) | 20,475 | ||
| Noncontrolling interests | (1,616 | ) | 1,806 | ||
| Total (deficit) equity | (9,382 | ) | 22,281 | ||
| Total liabilities and (deficit) equity | 7,063 | 34,140 | |||
| BEYONDSPRING INC. | ||||||||||||
| UNAUDITED INTERIM CONDENSED CONSOLIDATED STATEMENTS OF | ||||||||||||
| COMPREHENSIVE LOSS FOR THE THREE AND NINE MONTHS ENDED SEPTEMBER 30, 2018 AND 2019 | ||||||||||||
| (Amounts in thousands of U.S. Dollars (“$”), except for number of shares and per share data) | ||||||||||||
| (Unaudited) | ||||||||||||
| Three months ended | Nine months ended | |||||||||||
| September 30, | September 30, | |||||||||||
| 2018 | 2019 | 2018 | 2019 | |||||||||
| $ | $ | $ | $ | |||||||||
| Revenue | - | - | - | - | ||||||||
| Operating expenses | ||||||||||||
| Research and development | (14,123 | ) | (7,230 | ) | (39,191 | ) | (18,762 | ) | ||||
| General and administrative | (1,528 | ) | (2,474 | ) | (3,644 | ) | (6,260 | ) | ||||
| Loss from operations | (15,651 | ) | (9,704 | ) | (42,835 | ) | (25,022 | ) | ||||
| Foreign exchange loss, net | (321 | ) | (131 | ) | (449 | ) | (127 | ) | ||||
| Interest expense | - | (46 | ) | - | (186 | ) | ||||||
| Interest income | 77 | 57 | 205 | 64 | ||||||||
| Other income | - | - | 316 | - | ||||||||
| Loss before income tax | (15,895 | ) | (9,824 | ) | (42,763 | ) | (25,271 | ) | ||||
| Income tax benefit | - | - | - | - | ||||||||
| Net loss | (15,895 | ) | (9,824 | ) | (42,763 | ) | (25,271 | ) | ||||
| Less: Net loss attributable to | ||||||||||||
| noncontrolling interests | (965 | ) | (457 | ) | (2,011 | ) | (1,259 | ) | ||||
| Net loss attributable to | ||||||||||||
| BeyondSpring Inc. | (14,930 | ) | (9,367 | ) | (40,752 | ) | (24,012 | ) | ||||
| Net loss per share | ||||||||||||
| Basic and diluted | (0.65 | ) | (0.37 | ) | (1.81 | ) | (1.01 | ) | ||||
| Weighted-average shares outstanding | ||||||||||||
| Basic and diluted | 22,951,635 | 25,309,776 | 22,547,990 | 23,819,453 | ||||||||
| Other comprehensive loss, net of tax of nil: | ||||||||||||
| Foreign currency translation | ||||||||||||
| adjustment gain | 167 | 113 | 271 | 144 | ||||||||
| Comprehensive loss | (15,728 | ) | (9,711 | ) | (42,492 | ) | (25,127 | ) | ||||
| Less: Comprehensive loss attributable to | ||||||||||||
| noncontrolling interests | (953 | ) | (494 | ) | (1,977 | ) | (1,298 | ) | ||||
| Comprehensive loss attributable to | ||||||||||||
| BeyondSpring Inc. | (14,775 | ) | (9,217 | ) | (40,515 | ) | (23,829 | ) | ||||
| BEYONDSPRING INC. | |||||||||||||||
| UNAUDITED INTERIM CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS | |||||||||||||||
| FOR THE NINE MONTHS ENDED SEPTEMBER 30, 2018 AND 2019 | |||||||||||||||
| (Amounts in thousands of U.S. Dollars (“$”)) | |||||||||||||||
| (Unaudited) | |||||||||||||||
| Nine months ended September 30, | |||||||||||||||
| 2018 | 2019 | ||||||||||||||
| $ | $ | ||||||||||||||
| Operating activities: | |||||||||||||||
| Net loss | (42,763 | ) | (25,271 | ) | |||||||||||
| Adjustments to reconcile net loss to net cash from | |||||||||||||||
| operating activities: | |||||||||||||||
| Share-based compensation | 6,041 | 1,750 | |||||||||||||
| Depreciation expenses | 29 | 61 | |||||||||||||
| Other income from government grant | (307 | ) | - | ||||||||||||
| Changes in operating assets and liabilities: | |||||||||||||||
| Advances to suppliers | (321 | ) | (3,992 | ) | |||||||||||
| Due from related parties | - | 481 | |||||||||||||
| Prepaid expenses and other current assets | (209 | ) | (89 | ) | |||||||||||
| Operating lease right-of-use assets | - | 484 | |||||||||||||
| Other noncurrent assets | (296 | ) | (68 | ) | |||||||||||
| Accounts payable | (18 | ) | (7,638 | ) | |||||||||||
| Accrued expenses | 6,137 | (705 | ) | ||||||||||||
| Operating lease liabilities | - | (536 | ) | ||||||||||||
| Other current liabilities | 72 | 43 | |||||||||||||
| Net cash used in operating activities | (31,635 | ) | (35,480 | ) | |||||||||||
| Investing activities: | |||||||||||||||
| Acquisitions of property and equipment | (97 | ) | (4 | ) | |||||||||||
| Proceeds from maturity of short-term investments | 3,074 | - | |||||||||||||
| Net cash provided by (used in) investing activities | 2,977 | (4 | ) | ||||||||||||
| Financing activities: | |||||||||||||||
| Proceeds from issuance of ordinary shares, net of underwriting discounts and commissions | 14,000 | 44,957 | |||||||||||||
| Capital contributions from noncontrolling interests | - | 10,083 | |||||||||||||
| Payment of offering costs | (255 | ) | (318 | ) | |||||||||||
| Proceeds from loans | - | 2,986 | |||||||||||||
| Proceeds from related party borrowings | - | 3,328 | |||||||||||||
| Repayment of loans | - | (1,493 | ) | ||||||||||||
| Repayment of related party borrowings | - | (3,328 | ) | ||||||||||||
| Net cash provided by financing activities | 13,745 | 56,215 | |||||||||||||
| Effect of foreign exchange rate changes, net | 271 | 58 | |||||||||||||
| Net (decrease) increase in cash and cash equivalent | (14,642 | ) | 20,789 | ||||||||||||
| Cash and cash equivalent at beginning of period | 27,481 | 3,889 | |||||||||||||
| Cash and cash equivalent at end of period | 12,839 | 24,678 | |||||||||||||
Media Contact:
Caitlin Kasunich / Dave Schemelia
KCSA Strategic Communications
212.896.1241 / 212.896.1242
ckasunich@kcsa.com / dschemelia@kcsa.com