On May 11, 2020 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biotechnology company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported recent business highlights, anticipated upcoming milestones, and financial results for the first quarter of 2020 (Press release, BeiGene, MAY 11, 2020, View Source [SID1234557510]).
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"Our recent approval of tislelizumab in China for patients with previously treated locally advanced or metastatic urothelial carcinoma, as well as the positive readouts of two Phase 3 trials of tislelizumab for first-line non-small cell lung cancer at interim analyses, are key milestones for BeiGene as we execute on our goals and work to create impactful medicines that will be accessible to far more cancer patients around the world. With the COVID-19 pandemic continuing to create obstacles globally, our team has been quick to react as we work to minimize the impact and support our patients and physicians on the frontlines. We are managing the challenges to maintain momentum with our broad development program and are contributing to the global effort to fight the pandemic," said John V. Oyler, Co-Founder, Chief Executive Officer, and Chairman of BeiGene. "In addition to our launch of tislelizumab in China this quarter, we are on the way to having potentially up to 11 commercial products before the end of next year, and look forward to presenting Phase 3 data on BRUKINSA and tislelizumab at ASCO (Free ASCO Whitepaper). We also anticipate several additional Phase 3 or potentially registration-enabling studies reading out in the next 12 months."
Recent Business Highlights and Upcoming Milestones
Commercial Operations
Launched tislelizumab in China in March 2020 for patients with classical Hodgkin’s lymphoma (cHL) who have received at least two prior therapies;
Received approval from the China National Medical Products Administration (NMPA) for tislelizumab as a treatment for patients with previously treated locally advanced or metastatic urothelial carcinoma;
Generated $52.06 million in product revenue in the three months ended March 31, 2020;
As announced previously, the NMPA suspended the importation, sales and use of ABRAXANE (nanoparticle albumin-bound paclitaxel) in China supplied to BeiGene by Celgene Corporation, a Bristol Myers Squibb (BMS) company. As a result, Celgene initiated a voluntary recall of ABRAXANE in mainland China; and
Received commercial insurance reimbursement for tislelizumab as a treatment for relapsed/refractory classical Hodgkin’s lymphoma in Zhuhai, China.
Amgen Collaboration
Transition activities for the three Amgen commercial oncology medicines, XGEVA (denosumab), KYPROLIS (carfilzomib), and BLINCYTO (blinatumomab) in China are on track. BeiGene is preparing to commence promotional activities for XGEVA in patients with giant cell tumor of bone in the third quarter of 2020. Regulatory activities for KYPROLIS and BLINCYTO are in progress, with new drug applications (NDAs) to the NMPA submitted in the fourth quarter 2019. Additionally, a supplemental NDA for XGEVA for an expanded indication in skeletal-related events in China was accepted by the NMPA; and
BeiGene is working with Amgen to advance the clinical-stage oncology assets in the collaboration pursuant to the global development plan.
EUSA Collaboration
Regulatory discussions are in progress and biologics license applications (BLAs) in China for both SYLVANT (siltuximab) and QARZIBA▼ (dinutuximab beta) are expected to be submitted in 2020.
Clinical Programs
BRUKINSA (zanubrutinib), a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) designed to maximize BTK occupancy and minimize off-target effects; approved in the United States
Initiated a multi-center Phase 2 clinical trial (NCT04382586) evaluating zanubrutinib for the treatment of patients hospitalized for COVID-19 infection and pulmonary distress. The trial is designed to enroll approximately 42 patients, randomized to receive oral zanubrutinib at 320 mg once daily for 28 days plus supportive care, or placebo plus supportive care. An additional cohort of four to 10 patients on mechanical ventilation will all receive zanubrutinib plus
supportive care. The trial’s primary endpoint is the respiratory failure-free survival rate at day 28 in the randomized cohort.
Expected Milestones for Zanubrutinib
Receive approvals in China for the treatment of patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) and R/R chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in the first half of 2020;
Announce top-line results from the SEQUOIA trial comparing zanubrutinib with bendamustine plus rituximab in patients with treatment-naïve CLL or SLL as early as the second half of 2020;
File a supplemental new drug application (sNDA) in China for Waldenström’s macroglobulinemia (WM) in 2020;
Discuss data from the Phase 3 ASPEN trial (NCT03053440) comparing zanubrutinib to ibrutinib in patients with WM with the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) in 2020;
Complete expanded enrollment in the Phase 3 ALPINE trial (NCT03734016) comparing zanubrutinib with ibrutinib in patients with R/R CLL/SLL in 2020; and
Present data from Phase 3 ASPEN trial comparing zanubrutinib to ibrutinib in patients with WM in an oral presentation at the 2020 ASCO (Free ASCO Whitepaper) Virtual Science Program being held May 29-31, 2020, and present three-year follow-up data of treatment-naïve and previously treated patients with WM.
Tislelizumab, a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages; approved in China
Announced that the Center for Drug Evaluation (CDE) of the NMPA accepted an sNDA of tislelizumab in combination with two chemotherapy regimens for first-line treatment of patients with advanced squamous non-small cell lung cancer (NSCLC);
Announced that the pivotal Phase 3 trial (NCT03663205) of patients with first-line advanced non-squamous NSCLC met its primary endpoint at the planned interim analysis, demonstrating a statistically significant improvement in progression-free survival (PFS) for tislelizumab in combination with pemetrexed and platinum chemotherapy compared to pemetrexed and platinum chemotherapy alone as assessed by the independent review committee (IRC). The safety profile of tislelizumab in combination with pemetrexed and platinum chemotherapy was consistent with the known risks of each study treatment, and no new safety signals were identified;
Completed enrollment in the Phase 3 trial (NCT03358875) of tislelizumab versus docetaxel as a second- or third-line treatment in patients with NSCLC; and
Completed enrollment in the global Phase 3 trial (NCT03430843) of tislelizumab versus chemotherapy as a second-line treatment in patients with advanced esophageal squamous cell carcinoma (ESCC).
Expected Milestones for Tislelizumab
Submit an sNDA in China for first-line treatment of patients with advanced non-squamous NSCLC in 2020 and present data at an upcoming medical conference;
Have regulatory discussions with health authorities based on preliminary results from the global Phase 2 trial (NCT03419897) in second- or third-line patients with hepatocellular carcinoma (HCC) in 2020;
Present data from the Phase 3 trial in patients with first-line advanced squamous NSCLC at the 2020 ASCO (Free ASCO Whitepaper) Virtual Scientific Program;
Announce top-line results from the Phase 3 trial (NCT03358875) comparing tislelizumab versus docetaxel in second-or third-line patients with NSCLC and in the global Phase 3 trial (NCT03430843) comparing tislelizumab versus chemotherapy in second-line patients with advanced ESCC in 2020 or early 2021;
Initiate a Phase 3 trial in China for patients with resectable Stage II or IIIA NSCLC; and
Complete enrollment in the pivotal Phase 2 trial (NCT03736889) in China of patients with mismatched repair deficient (dMMR) or microsatellite instability-high (MSI-H) solid tumors in 2020.
Pamiparib, an investigational selective small molecule inhibitor of PARP1 and PARP2
Completed enrollment in the Phase 2 clinical trial (NCT03575065) in China in patients with advanced HER2-negative breast cancer harboring germline BRCA mutation that have progressed despite standard therapy or for which no standard therapy exists.
Expected Milestones for Pamiparib
Have regulatory discussions based on preliminary results from the Phase 2 trial (NCT03333915) in Chinese patients with third-line and above previously treated ovarian cancer (OC) harboring germline BRCA 1/2 mutations, and potentially submit an NDA in China in 2020;
Announce top-line results from the Phase 3 trial (NCT03519230) of pamiparib as a maintenance treatment in patients with platinum-sensitive recurrent OC in 2020 or the first half of 2021; and
Present updated data from the Phase 1 trial (NCT02660034) of pamiparib in combination with tislelizumab in patients with advanced solid tumors in 2020.
Lifirafenib, an investigational RAF dimer inhibitor
Published Phase 1 data in the Journal of Clinical Oncology.
BGB-A1217, an investigational TIGIT monoclonal antibody
Expected Milestones for BGB-A1217
Present clinical data from the Phase 1 trial in 2020 or early 2021.
BGB-11417, an investigational small molecule Bcl-2 inhibitor
Initiated patient enrollment for the Phase 1 trial (NCT04277637) of BGB-11417 in patients with mature B-cell malignancies. We intend to develop BGB-11417 both as a monotherapy and in combination with zanubrutinib.
Collaboration Programs
Sitravatinib, an investigational tyrosine kinase inhibitor of receptor tyrosine kinases (RTKs), including TAM family receptors (TYRO3, Axl, MER), split family receptors (VEGFR2, KIT) and RET, licensed from Mirati Therapeutics in Asia (excluding Japan), Australia, and New Zealand
Expected Milestones for Sitravatinib
Present additional Phase 1 clinical data on sitravatinib combined with tislelizumab at a medical meeting in 2020.
ZW25, a novel investigational Azymetric bispecific antibody currently in Phase 2 clinical development with Zymeworks, Inc.
Initiated enrollment in a two-arm Phase 1b/2 trial (NCT04276493) evaluating ZW25 in combination with chemotherapy as a first-line treatment for patients with metastatic HER2-positive breast cancer and in combination with chemotherapy and tislelizumab as a first-line treatment for patients with metastatic HER2-positive gastroesophageal adenocarcinoma (GEA).
Expected Milestones for ZW25
Support clinical development and enrollment of the planned registration-enabling trials in refractory HER2-positive biliary tract cancer in 2020 and first-line HER2-positive gastroesophageal adenocarcinomas in late 2020 or early 2021.
BGB-3245, an investigational RAF dimer inhibitor with activity against mutant monomeric and dimeric forms of B-RAF in preclinical studies. BGB-3245 is being developed by MapKure, which BeiGene jointly owns with SpringWorks Therapeutics
Announced that the first patient has been dosed in Australia in the Phase 1 clinical trial (NCT04249843) in patients with advanced or refractory solid tumors. The U.S. FDA has allowed the Investigational New Drug (IND) application submitted for BGB-3245 to proceed, which will enable study expansion to U.S. sites.
Manufacturing Facilities
Completed equipment validation and executed manufacturing process validation for the first phase of our manufacturing facility in Guangzhou; and
Began construction of the second phase of our manufacturing facility in Guangzhou to significantly increase manufacturing capacity, expected to be completed by the end of 2020.
COVID-19 Impact and Response
The Company expects that the worldwide health crisis of COVID-19 will have a negative impact on its operations, including commercial sales, regulatory interactions and inspections, and clinical trial recruitment and participation. The impact on the Company’s operations in China has started to alleviate, as much of the country gradually resumes regular business. The Company is working to continue to minimize delays and disruptions and continues to execute on its commercialization, regulatory and clinical development goals globally.
In addition to the clinical trial of zanubrutinib in COVID-19 patients, the Company announced plans to work with Atreca, Inc. and IGM Biosciences, Inc. to leverage the parties’ technology and expertise in an effort to discover, develop, and manufacture novel IgM or IgA antibodies targeting SARS-CoV-2 for the potential treatment of COVID-19.
First Quarter 2020 Financial Results
Cash, Cash Equivalents, Restricted Cash, and Short-Term Investments were $3.38 billion as of March 31, 2020, compared to $985.50 million as of December 31, 2019.
Total cash and short-term investments increased $2.39 billion in the three months ended March 31, 2020, primarily due to the $2.78 billion of cash received from the sale of American Depositary Shares to Amgen in connection with the closing of the Amgen collaboration on January 2, 2020. In the three months ended March 31, 2020, cash used in operating activities totaled $341.94 million, capital expenditures were $21.53 million, and cash used for upfront license payments totaled $43.00 million.
Revenue for the three months ended March 31, 2020 was $52.06 million, compared to $77.83 million in the same period of 2019. The decrease in total revenue is primarily attributable to the lack of collaboration revenue after the termination of the Celgene collaboration agreement for tislelizumab and decreased product sales of ABRAXANE, REVLIMID (lenalidomide) and VIDAZA (azacitidine) in China, partially offset by the initial sales of tislelizumab in China and BRUKINSA in the United States.
Product revenues totaled $52.06 million for the three months ended March 31, 2020, compared to $57.42 million for the three months ended March 31, 2019, and were comprised of:
Product revenue of $20.53 million from sales of tislelizumab in China since its launch in March 2020, including launch inventory build at distributors. Despite the challenges posed by COVID-19, the China commercial team launched tislelizumab on plan in the first quarter through efforts in multiple channels including extensive online promotion;
Product revenue of $30.82 million from sales of ABRAXANE, REVLIMID and VIDAZA in China, compared to $57.42 million in the same period of the prior year. The decrease in revenues was due to the negative impact of the COVID-19 pandemic, increased generic competition, and the suspension of ABRAXANE sales in China by the NMPA in March 2020; and
Product revenue of $0.72 million from sales of BRUKINSA in the United States. Early launch indicators including new patient starts, reimbursement coverage, and physician perception have been encouraging.
Collaboration revenue totaled nil for the three months ended March 31, 2020, compared to $20.41 million for the three months ended March 31, 2019.
Expenses for the three months ended March 31, 2020 were $425.82 million, compared to $251.59 million in the same period of 2019.
Cost of sales for the three months ended March 31, 2020 were $14.15 million, compared to $15.26 million in the same period of 2019. Cost of sales primarily includes acquisition costs related to the amount of ABRAXANE, REVLIMID and VIDAZA that was sold during the period in China, as well as the post-approval cost of tislelizumab and BRUKINSA that was sold during the period.
R&D Expenses for the three months ended March 31, 2020 were $304.30 million, compared to $178.35 million in the same period of 2019. The increase in R&D expenses was primarily attributable to continued increases in spending on our ongoing and newly initiated late-stage pivotal clinical trials, development expenses associated with the Amgen collaboration, the preparation for additional regulatory submissions, and manufacturing costs related to pre-commercial activities and supply. R&D expense in the three months ended March 31, 2020 also included $43.00 million of expense related to upfront license payments, compared to $10.00 million in the same period of 2019. Our co-funding obligation for the development of the pipeline assets under the Amgen collaboration for the three months ended March 31, 2020 was $56.00 million, of which $28.37 million was recorded as R&D expense. The remaining $27.63 million was recorded as a reduction of the R&D cost share liability. R&D-related share-based compensation expense was $20.40 million for the three months ended March 31, 2020, compared to $15.77 million for the same period of 2019.
SG&A Expenses for the three months ended March 31, 2020 were $107.08 million, compared to $57.65 million in the same period in 2019. The increase in SG&A expenses was primarily attributable to increased headcount, including the expansion of our commercial team to support the distribution of our commercial products in China and the United States, as well as higher professional service fees and costs to support our growing operations. SG&A-related share-based compensation expense was $17.86 million for the three months ended March 31, 2020, compared to $10.62 million for the same period of 2019.
Net Loss for the three months ended March 31, 2020 was $363.74 million, or $0.36 per share, or $4.70 per American Depositary Share (ADS), compared to $167.64 million, or $0.22 per share, or $2.81 per ADS in the same period in 2019.