FDA Submission to Change the Primary Endpoint for Study 106 Phase 3 into an Industry First and Robust Clinical Measure to Evaluate Superiority in CIN
- FDA Submission to Change the Primary Endpoint for Study 106 Phase 3 into an Industry First and Robust Clinical Measure to Evaluate Superiority in CIN
- Initiated NDA Rolling Submission for Plinabulin for CIN in China in Q1 2020
- On Track to Report Interim Analysis of Study 106 Phase 3 in Q2 2020 to Evaluate Superiority in CIN and Submit NDA for CIN in the U.S. in H2 2020
NEW YORK, April 30, 2020 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (the “Company” or “BeyondSpring”) (NASDAQ: BYSI), a global biopharmaceutical company focused on the development of innovative cancer therapies, announced today its financial results and provided an operational update for the three months and year ended December 31, 2019.
“In 2019, BeyondSpring transitioned into a late-stage development company with clear paths toward registration in two distinct, underserved patient populations for our first-in-class agent Plinabulin,” said Dr. Lan Huang, Co-Founder, Chairman and Chief Executive Officer of BeyondSpring. “Plinabulin is a potent antigen-presenting cell (APC) inducer, and we consider it a ‘pipeline in a drug.’ With approximately 1,000 patients enrolled globally for Plinabulin studies, we have a clear vision of additional indications for which Plinabulin can be applied. It starts with the foundational indication in CIN, then in NSCLC, and the future potential is in the triple combination with PD-1/PD-L1 antibodies and radiation or chemotherapy. In addition to Plinabulin, we are developing three pre-clinical immune agents and an R&D platform in ubiquitination protein degradation.”
“Importantly, we have demonstrated the benefit of Plinabulin in the prevention of CIN in five clinical studies,” continued Dr. Huang. “This data has been presented at several premier scientific conferences all over the world. With our upcoming interim data readout for Study 106 Phase 3 to evaluate superiority in CIN with Plinabulin in combination with G-CSF versus G-CSF alone as the standard of care (which has over $9 billion annual sales globally by itself), Plinabulin has the potential to effectively raise cancer patients’ neutrophil counts after chemotherapy use and prevent infection and hospitalization. We believe that Plinabulin will emerge as a transformative new therapy for the millions of cancer patients in dire need of a superior CIN prevention option and result in an improved quality of life. Our proprietary market research with over 100 practicing oncologists in the U.S. indicates that more than 70 percent of oncologists strongly favor the Plinabulin-G-CSF combination over monotherapy, and 65 percent said that they were highly likely to use the combination for the benefit of their patients. The results of our efforts in 2019 have well-positioned BeyondSpring for the next 12 months, enabling us to leverage the regulatory milestones in multiple NDA filings in China and the U.S., the two largest pharmaceutical markets in the world.”
Recent Operational Highlights
Chemotherapy Induced Neutropenia (CIN)
Plinabulin’s Effect in Preventing CIN Demonstrated in Five Clinical Trials So Far
- In the Phase 2 portion of Study 101, Plinabulin reduced the incidence of Grade 4 neutropenia from 33.8 percent in the docetaxel arm to less than 5 percent in the Plinabulin + docetaxel arms (p<0.0003) on Day 8 of the first cycle of chemotherapy.
- In the 138 patients in Study 103, Plinabulin reduced the incidence of Grade 4 neutropenia from 27.4 percent in the docetaxel arm to 3.1 percent in the Plinabulin + docetaxel arm (p<0.0001) on Day 8 of the first cycle of chemotherapy.
- In the Phase 2 portion of Study 105, both Plinabulin and Neulasta had a 14 percent incidence of Grade 4 neutropenia, but Plinabulin demonstrated a superior safety profile, with less bone pain, thrombocytopenia and immune suppression.
- In the interim analysis of the Phase 3 portion of Study 105, Plinabulin achieved non-inferior duration of severe neutropenia (DSN) and more rapid onset of action compared with Neulasta.
- In the Phase 2 portion of Study 106, Plinabulin + Neulasta demonstrated not only CIN efficacy superiority by increasing the rate of prevention of Grade 4 neutropenia to 62.5 percent from 40.9 percent in Neulasta monotherapy (a 53 percent increase), but also a superior safety profile with less bone pain, enabling patients to stay on the optimal dose of chemotherapy.
Study 106: Evaluating Superiority in CIN with Plinabulin + Neulasta versus Neulasta in Breast Cancer Treated with TAC
- BeyondSpring’s Phase 3 portion of Study 106, which evaluates Plinabulin in combination with Neulasta for the prevention of CIN, enrolled the first patient in October 2019. The trial expects to enroll a total of 222 patients, with a pre-specified interim analysis expected in Q2 2020 and final analysis expected in H2 2020.
- In April 2020, following discussions with the U.S. Food and Drug Administration (FDA), BeyondSpring changed the primary endpoint for the Phase 3 portion of Study 106. The new primary endpoint will be “the rate of prevention of Grade 4 neutropenia in the first cycle of chemotherapy” – a more clinically meaningful and trial-sensitive endpoint – and will be used to evaluate superiority of the Plinabulin-G-CSF combination over G-CSF alone in CIN prevention. A robust plan will be submitted to the FDA to validate this new primary endpoint against clinical outcome measures.
Study 105: Evaluating Non-inferiority in CIN with Plinabulin versus Neulasta in Various Cancers Treated with Docetaxel
- The Phase 3 portion of Study 105, which evaluates Plinabulin as a monotherapy for the prevention of CIN, has enrolled 105 patients at a pre-specified interim analysis in which it achieved statistical significance in the primary endpoint of DSN in the first cycle of chemotherapy. It expects to enroll the remaining 45 patients in H2 2020 in a trial with a total expected enrollment of 150 patients. The final analysis of this trial is expected in H2 2020.
BeyondSpring Initiates NDA Rolling Submission for Plinabulin for CIN in China
- In March 2020, BeyondSpring reported that it had initiated the rolling submission of its New Drug Application (NDA) with Plinabulin for the CIN indication to China’s National Medical Products Administration (NMPA). If approved, Plinabulin, in combination with G-CSFs, would represent the first superior therapy to the standard of care, with a broad label for CIN prevention after all chemotherapies, in all cancer types, in combination with all G-CSFs. The Company expects to submit an NDA for the same indication to the FDA in H2 2020.
Non-Small Cell Lung Cancer (NSCLC)
- The Company’s Study 103 is a 554-patient Phase 3 trial for Plinabulin, in combination with docetaxel, for the treatment of second- / third-line EGFR wild-type NSCLC. The final analysis of the trial is expected in H2 2020.
- Thus far, over 600 cancer patients who have been dosed with Plinabulin have shown good tolerability, which satisfies the safety database standard of both the FDA and NMPA.
Mechanism of Action (MoA)
Publications in 2019
- Differentiated tubulin binding pocket and distinct kinetics (Chem 2019; 5:1-18)
- DC maturation by releasing GEF-H1 and T cell activation (Cell Reports 2019; 28:3367-3380)
- CIN mechanism in bone marrow protection and effect in multiple chemotherapies (Cancer Chemotherapy and Pharmacology 2019; 85:461-468)
- Distinct anti-tumor effect in KRAS mutant model and brain tumor model as monotherapy (Biomedical Reports 2019; 10:218-224)
Plinabulin’s Early Protection of Neutrophil and Rapid Onset of Action Complementary to G-CSFs
- In April 2020, BeyondSpring reported that Plinabulin protects against CIN during Week 1 of the first chemotherapy cycle, consistent with a rapid onset MoA. In contrast, Neulasta as a single agent offers neutrophil protection beginning Week 2, consistent with a late onset. The rate of prevention of Grade 4 neutropenia in Cycle, 1 Day 1 to Day 8 for arms with Plinabulin use (n=93) was 68.8 percent versus 40.9 percent with the Neulasta 6 mg monotherapy arm (n=22) (p=0.0149) in the Phase 2 portion of Study 106. Rapid onset of protection was also seen in Study 105. Because of their complementary onset of CIN protection and mechanisms of action, combining the two agents together offered superior and maximum protection throughout the entire chemotherapy cycle.
Plinabulin Stimulates the Innate and Adaptive Immune System
- In March 2020, BeyondSpring presented new data as a poster at the National Comprehensive Cancer Network (NCCN) Annual Conference that highlighted Plinabulin’s potential ability to prevent tissue iron overload, a common cause of vital organ damage in cancer patients receiving chronic blood transfusions as a result of their chemotherapy. Plinabulin is a potent inducer of the immune-modulatory protein haptoglobin, which could restore its rapid depletion during blood transfusions.
- In February 2020, BeyondSpring presented a poster at the ASCO-SITC Clinical Immuno-Oncology Symposium demonstrating Plinabulin’s ability to potently stimulate the innate immune system by increasing plasma levels of both the neutrophil count and haptoglobin. Plinabulin’s dual ability to stimulate the adaptive and innate immune system is valuable for its use in preventing CIN and treating cancer.
Intellectual Properties
- For all assets, BeyondSpring owns or co-owns 81 patents in 36 jurisdictions, including 20 issued U.S. patents.
- For Plinabulin and its analogs, the Company owns 74 patents, including 16 issued U.S. patents, with protection through 2036.
BeyondSpring Granted U.S. Patent for Plinabulin-Taxane Combination Cancer Treatment
- In April 2020, the U.S. Patent and Trademark Office (USPTO) granted BeyondSpring a patent for the Plinabulin-Taxane combination to reduce docetaxel-induced severe neutropenia. This represents the first of a series of patents protecting Plinabulin’s novel effect in reducing CIN.
BeyondSpring Submits for U.S. Patent on Methods of Treating Viral Infections, Including COVID-19
- In March 2020, BeyondSpring submitted for a provisional U.S. patent application for the Company’s pipeline asset, BPI-002, for methods of treating viral infections, including COVID-19, when administered alone or in combination with a vaccine. BPI-002 can potentially activate the adaptive immune system to directly attack and kill virally infected cells. If combined with a vaccine, BPI-002 can also potentially function as an adjuvant to provide improved long-term humoral protection against future viral infections.
Financial Results for the Three Months Ended December 31, 2019
Research and development (“R&D”) expenses were $12.6 million for the quarter ended December 31, 2019, compared to $13.3 million for the quarter ended December 31, 2018. The $0.7 million decrease was largely attributable to a decrease of $0.5 million in clinical trial expenses and a decrease of $0.2 million in non-cash share-based compensation.
General and administrative (“G&A”) expenses were $2.7 million for the quarter ended December 31, 2019, compared to $2.3 million for the quarter ended December 31, 2018. The $0.4 million increase was mainly due to the increase of employee salaries and welfares.
Net loss attributable to the Company was $14.1 million for the quarter ended December 31, 2019, compared to $14.7 million for the quarter ended December 31, 2018.
Financial Results for the Twelve Months Ended December 31, 2019
Research and development (“R&D”) expenses were $31.3 million for the year ended December 31, 2019, compared to $51.6 million for the year ended December 31, 2018. The $20.3 million decrease was largely attributable to a decrease of $9.4 million in clinical trial expenses, a decrease of $6.2 million in non-cash share-based compensation and a decrease of $5.0 million in consultant and other expenses.
General and administrative (“G&A”) expenses were $9.0 million for the year ended December 31, 2019, compared to $5.9 million for the year ended December 31, 2018. The $3.1 million increase was mainly due to an increase of $1.7 million in non-cash share-based compensation expenses, an increase of $1.1 million in professional service fees and an increase of $1.0 million in salaries and welfare benefits.
Net loss attributable to the Company was $40.3 million for the year ended December 31, 2019, compared to $57.5 million for the year ended December 31, 2018.
As of December 31, 2019, the Company had a cash balance of $35.9 million. The Company believes that it has sufficient cash to support its clinical trials and submit NDAs in the U.S. and China for Plinabulin for the CIN and NSCLC indications, as well as to advance its immuno-oncology pipeline and ubiquitination protein degradation research platform.
Anticipated Milestones
The following outlines the Company’s anticipated upcoming milestones and projected timelines:
- Interim data readout for Study 106 Phase 3 for CIN – Q2 2020
- Final data readout for Study 106 Phase 3 for CIN – H2 2020
- Final data readout for Study 105 Phase 3 for CIN – H2 2020
- NDA submission for Plinabulin for CIN in the U.S. – H2 2020
- Final data readout for Study 103 Phase 3 for NSCLC – H2 2020
- NDA submission for Plinabulin for NSCLC in China – H2 2020
- NDA submission for Plinabulin for NSCLC in the U.S. – 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 1-855-327-6837 (U.S.) or 1-631-891-4304 (international). Please reference conference ID: 10009417. 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, first-in-class agent Plinabulin, 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.
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, difficulties raising the anticipated amount needed to finance the Company’s future operations on terms acceptable to the Company, if at all, unexpected results of clinical trials, delays or denial in regulatory approval process, results that do not meet our expectations regarding the potential safety, the ultimate efficacy or clinical utility of our product candidates, increased competition in the market, and other risks described in BeyondSpring’s most recent Form 20-F on file with the U.S. Securities and Exchange Commission. All 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. | ||||
| CONSOLIDATED BALANCE SHEETS | ||||
| (Amounts in thousands of U.S. Dollars (“$”), except for number of shares and per share data) | ||||
| As ofDecember 31, | ||||
| 2018 | 2019 | |||
| $ | $ | |||
| Assets | ||||
| Current assets: | ||||
| Cash and cash equivalents | 3,889 | 35,933 | ||
| Advances to suppliers | 1,209 | 4,519 | ||
| Due from related parties | 481 | - | ||
| Prepaid expenses and other current assets | 292 | 410 | ||
| Total current assets | 5,871 | 40,862 | ||
| Noncurrent assets: | ||||
| Property and equipment, net | 282 | 209 | ||
| Operating lease right-of-use assets | - | 2,538 | ||
| Other noncurrent assets | 910 | 946 | ||
| Total noncurrent assets | 1,192 | 3,693 | ||
| Total assets | 7,063 | 44,555 | ||
| Liabilities and equity | ||||
| Current liabilities: | ||||
| Accounts payable | 9,586 | 2,537 | ||
| Accrued expenses | 5,495 | 5,861 | ||
| Current portion of operating lease liabilities | - | 537 | ||
| Due to related parties | - | 29 | ||
| Other current liabilities | 1,364 | 1,089 | ||
| Total current liabilities | 16,445 | 10,053 | ||
| Noncurrent liabilities: | ||||
| Long-term loans | - | 1,436 | ||
| Operating lease liabilities | - | 1,935 | ||
| Total noncurrent liabilities | - | 3,371 | ||
| Total liabilities | 16,445 | 13,424 | ||
| Commitments and contingencies | ||||
| BEYONDSPRING INC. | |||||
| CONSOLIDATED BALANCE SHEETS | |||||
| (Amounts in thousands of U.S. Dollars (“$”), except for number of shares and per share data) | |||||
| As ofDecember 31, | |||||
| 2018 | 2019 | ||||
| $ | $ | ||||
| Equity (deficit): | |||||
| Ordinary shares ($0.0001 par value; 500,000,000 shares | |||||
| authorized; 23,184,612 shares and 27,885,613 | |||||
| shares issued and outstanding as of December 31, | |||||
| 2018 and 2019, respectively) | 2 | 3 | |||
| Additional paid-in capital | 170,950 | 246,979 | |||
| Accumulated deficit | (178,760 | ) | (216,845 | ) | |
| Accumulated other comprehensive income | 42 | 140 | |||
| Total BeyondSpring Inc. shareholders’ (deficit) equity | (7,766 | ) | 30,277 | ||
| Noncontrolling interests | (1,616 | ) | 854 | ||
| Total (deficit) equity | (9,382 | ) | 31,131 | ||
| Total liabilities and equity (deficit) | 7,063 | 44,555 | |||
| BEYONDSPRING INC. | ||||||||||||
| CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS FOR THE THREE MONTHS | ||||||||||||
| (UNAUDITED) AND YEAR ENDED DECEMBER 31, 2018 AND 2019 | ||||||||||||
| (Amounts in thousands of U.S. Dollars (“$”), except for number of shares and per share data) | ||||||||||||
| (Unaudited) | ||||||||||||
| Three months ended | Twelve months ended | |||||||||||
| December 31, | December 31, | |||||||||||
| 2018 | 2019 | 2018 | 2019 | |||||||||
| $ | $ | $ | $ | |||||||||
| Revenue | - | - | - | - | ||||||||
| Operating expenses | ||||||||||||
| Research and development | (13,295 | ) | (12,580 | ) | (51,618 | ) | (31,342 | ) | ||||
| General and administrative | (2,283 | ) | (2,705 | ) | (5,927 | ) | (8,965 | ) | ||||
| Loss from operations | (15,578 | ) | (15,285 | ) | (57,545 | ) | (40,307 | ) | ||||
| Foreign exchange gain (loss), net | (6 | ) | 123 | (455 | ) | (4 | ) | |||||
| Interest expense | - | (20 | ) | - | (206 | ) | ||||||
| Interest income | 5 | 120 | 211 | 184 | ||||||||
| Other income (expenses) | (1 | ) | - | 315 | - | |||||||
| Loss before income tax | (15,580 | ) | (15,062 | ) | (57,474 | ) | (40,333 | ) | ||||
| Income tax benefit | - | - | - | - | ||||||||
| Net loss | (15,580 | ) | (15,062 | ) | (57,474 | ) | (40,333 | ) | ||||
| Less: Net loss attributable to | ||||||||||||
| noncontrolling interests | (854 | ) | (989 | ) | (2,605 | ) | (2,248 | ) | ||||
| Net loss attributable to | ||||||||||||
| BeyondSpring Inc. | (14,726 | ) | (14,073 | ) | (54,869 | ) | (38,085 | ) | ||||
| Net loss per share | ||||||||||||
| Basic and diluted | (0.64 | ) | (0.52 | ) | (2.42 | ) | (1.55 | ) | ||||
| Weighted-average shares outstanding | ||||||||||||
| Basic and diluted | 23,013,265 | 27,097,553 | 22,665,265 | 24,645,714 | ||||||||
| Other comprehensive loss, net of tax of nil: | ||||||||||||
| Foreign currency translation | ||||||||||||
| adjustment gain | (12 | ) | (48 | ) | 251 | 96 | ||||||
| Comprehensive loss | (15,592 | ) | (15,110 | ) | (57,223 | ) | (40,237 | ) | ||||
| Less: Comprehensive loss attributable to | ||||||||||||
| noncontrolling interests | (859 | ) | (952 | ) | (2,578 | ) | (2,250 | ) | ||||
| Comprehensive loss attributable to | ||||||||||||
| BeyondSpring Inc. | (14,733 | ) | (14,158 | ) | (54,645 | ) | (37,987 | ) | ||||
Contacts
Jeffrey Goldberger / Caitlin Kasunich
KCSA Strategic Communications
212.896.1249 / 212.896.1241
jgoldberger@kcsa.com / ckasunich@kcsa.com
