On March 2, 2020 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical 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 fourth quarter and full year of 2019 (Press release, BeiGene, MAR 2, 2020, View Source [SID1234555056]).

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"Having co-founded BeiGene in 2010 with Dr. Xiaodong Wang, this anniversary year promises to continue the momentum and trajectory from our recent catalysts, including the read-outs of two Phase 3 trials, approvals for BRUKINSA and tislelizumab in the United States and China, respectively, and closing on our collaboration with Amgen, which is already off to a productive start as we advance the commercialization and development plans for Amgen’s three commercial-stage drugs and 20 drug candidates," said John V. Oyler, Co-Founder, Chief Executive Officer, and Chairman of BeiGene. "In the next two years, we expect to launch up to eight products and see continued robust clinical progress with the potential readout of more than 10 Phase 3 or potentially registration-enabling studies. Our earlier stage pipeline is also advancing with several internally developed or in-licensed drug candidates entering the clinic or reporting proof of concept data."

"Despite challenges to our business in China caused by the coronavirus outbreak (COVID-19), our team has continued to advance our programs and serve our patients. BeiGene took immediate safety measures to protect our staff in Wuhan and elsewhere and our employees are safe. In addition, we were one of the first companies to source and deliver donated safety equipment to major hospitals in the area. While we expect our broad business operations in China to be impacted by COVID-19, we continue to execute towards our tislelizumab launch goal in the first quarter this year," said Dr. Xiaobin Wu, General Manager of China and President of BeiGene.
Recent Business Highlights and Upcoming Milestones
Commercial Operations

Received accelerated approval from the U.S. Food and Drug Administration (FDA) of BRUKINSA (zanubrutinib) as a treatment for mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy; and launched within one week of approval;

Received approval from the China National Medical Products Administration (NMPA) of tislelizumab as a treatment for patients with classical Hodgkin’s lymphoma (cHL) who have received at least two prior therapies, with launch planned this month;

Generated $222.60 million in product revenue in the 12 months ended December 31, 2019, primarily from sales in China of ABRAXANE, REVLIMID, and VIDAZA, which represents a 70.1% increase compared to the same period in 2018. Revenue for the quarter ended December 31, 2019 was $56.89 million. BeiGene markets ABRAXANE, REVLIMID, and VIDAZA in China under an exclusive license from Celgene Logistics Sàrl, a Bristol-Myers Squibb company;

Submitted to the NMPA a supplemental new drug application (sNDA) for REVLIMID (lenalidomide), in combination with rituximab, for the treatment of patients with relapsed or refractory (R/R) indolent lymphoma (follicular lymphoma or marginal zone lymphoma). The sNDA has been accepted and granted priority review; and

ABRAXANE was included in the National Healthcare Security Administration of China’s volume-based procurement list, effective in the second quarter of 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

Announced results of the Phase 3 ASPEN trial (NCT03053440) comparing BRUKINSA to ibrutinib for the treatment of Waldenström’s macroglobulinemia (WM). While the primary endpoint of statistical superiority related to deep response (VGPR or better) was not met, zanubrutinib demonstrated more frequent VGPRs (28.4% vs.19.2% in overall population) and advantages in safety and tolerability compared to ibrutinib. ASPEN is the largest Phase 3 trial in WM conducted to-date and the first comparative trial readout for BTK inhibitors;

Completed enrollment in the Phase 2 MAGNOLIA trial (NCT03846427) in patients with R/R marginal zone lymphoma (MZL);

Presented clinical data on BRUKINSA at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, including:

Initial results presented in an oral session of the SEQUOIA trial (NCT03336333) Arm C in patients with treatment-naïve (TN) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with Del(17p);

Updated results presented in an oral session of the Phase 1/2 trial (NCT02343120) in patients with CLL or SLL;

Updated results presented in a poster from the Phase 1b trial (NCT02795182) of BRUKINSA in combination with tislelizumab in patients with previously treated B-cell lymphoid malignancies; and

Initiated a Phase 1/2 clinical trial in Japan of zanubrutinib in patients with mature B-cell malignancies.
Expected Milestones for Zanubrutinib

Receive approvals in China for the treatment of patients with R/R MCL and R/R CLL/SLL in the first half of 2020;

Announce top-line results from the SEQUOIA trial comparing zanubrutinib with bendamustine plus rituximab in patients with TN CLL or SLL as early as the second half of 2020;

File an sNDA in China for WM in 2020;

Discuss ASPEN data with U.S. FDA and European Medicines Agency (EMA) and present Phase 3 ASPEN data at a major medical conference in 2020; and

Complete expanded enrollment in the Phase 3 ALPINE trial comparing zanubrutinib with ibrutinib in patients with R/R CLL/SLL in 2020.
Tislelizumab, a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages; approved in China

Announced that the pivotal Phase 3 trial (NCT 03594747) of tislelizumab in combination with chemotherapy for the first-line treatment of patients with squamous non-small cell lung cancer (NSCLC) met the primary endpoint of improved progression-free survival (PFS) at the pre-planned interim analysis, as assessed by independent review committee (IRC). The safety profile of tislelizumab in both combinations in this trial was consistent with the known risks of each study treatment, and no new safety signals were identified;

Received orphan-drug designation for tislelizumab from the U.S. FDA for hepatocellular carcinoma (HCC) and esophageal squamous cell carcinoma (ESCC); and

Announced updated clinical results presented at the ESMO (Free ESMO Whitepaper) Asia 2019 Congress from the Phase 2 trial (NCT03469557) of tislelizumab in combination with chemotherapy in patients with gastric/ gastroesophageal junction (G/GEJ) adenocarcinoma or ESCC.
Expected Milestones for Tislelizumab

Receive approval in China for the treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) in 2020;

Submit sNDA for the first-line treatment of patients with squamous NSCLC in China in 2020;

Have regulatory discussions with health authorities based on preliminary results from the global Phase 2 trial (NCT03419897) of tislelizumab in second- or third-line patients with HCC in 2020;

Announce top-line results from the Phase 3 trial (NCT03663205) comparing tislelizumab plus chemotherapy to chemotherapy alone in first-line patients with non-squamous NSCLC in China in 2020;

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; and

Complete enrollment in the global portion of the Phase 3 trial (NCT03358875) comparing tislelizumab with docetaxel in second-or third-line patients with NSCLC and in the global Phase 3 trial (NCT03430843) comparing tislelizumab

with chemotherapy in second-line patients with advanced ESCC in early 2020 and announce top-line results in 2020 or early 2021.
Pamiparib, an investigational selective small molecule inhibitor of PARP1 and PARP2

Disclosed plans to convert from Phase 3 to Phase 2 the clinical trial of pamiparib vs. placebo as maintenance therapy in patients with inoperable locally advanced or metastatic gastric cancer who have responded to platinum-based first line chemotherapy (NCT 03427814; also known as the BGB-290-303 trial). The Company plans to evaluate data from the Phase 2 trial to assess the potential of pamiparib in this indication and the potential next steps of development as a monotherapy or in combination with other therapies.
Expected Milestones for Pamiparib

Have regulatory discussions based on preliminary results from the Phase 2 trial (NCT03333915) in Chinese patients with third or later line previously treated ovarian cancer (OC) harboring germline BRCA 1/2 mutations and potentially submit a new drug application (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 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.
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

Presented clinical data in an oral session at the European Society for Medical Oncology Immuno-Oncology (ESMO-IO) Congress in December 2019 from the Phase 1b trial (NCT03666143) of sitravatinib combined with tislelizumab in patients with platinum-resistant OC.
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.
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; and

Initiate a Phase 1b/2 trial investigating ZW25 in combination with chemotherapy with and without tislelizumab in patients with advanced HER2-positive breast cancer or gastric/gastroesophageal junction adenocarcinoma in early 2020.
Lifirafenib, an investigational RAF dimer inhibitor
Expected Milestones for Lifirafenib

Publish Phase 1 data in a peer-reviewed journal in 2020.
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-A445, an investigational non-ligand competing anti OX40 agonistic monoclonal antibody

Initiated a Phase 1 trial (NCT04215978) of BGB-A445 as monotherapy and in combination with tislelizumab in patients with advanced solid tumors.

BGB-3245, an investigational B-RAF inhibitor with activity against mutant monomeric and dimeric forms of B-RAF in pre-clinical studies. BGB-3245 is being developed by MapKure, which BeiGene jointly owns with SpringWorks Therapeutics

Initiated a Phase 1 clinical trial (NCT04249843) in patients with advanced or refractory tumors harboring specific v-RAF murine sarcoma viral oncogene homolog B (B-RAF) genetic mutations.
BGB-11417, an investigational small molecule Bcl-2 inhibitor

Initiated study start-up for a Phase 1 trial in Australia and the United States in patients with mature B-cell malignancies.
Expected Milestones for BGB-11417

Begin patient enrollment for the Phase 1 trial in mature B-cell malignancies in the first quarter or early in the second quarter of 2020.
Manufacturing Facilities

Received a drug manufacturing license for our Guangzhou biologics manufacturing facility in December 2019;

Initiated tislelizumab manufacturing process validation; and

Began Phase 2 expansion for additional manufacturing capacity at our Guangzhou manufacturing facility, expected to be completed by the end of 2020.
Corporate Developments

Closed the global strategic collaboration with Amgen to commercialize XGEVA (denosumab), KYPROLIS (carfilzomib), and BLINCYTO (blinatumomab) in China and jointly develop 20 Amgen oncology pipeline assets. Amgen purchased approximately $2.8 billion of BeiGene’s American Depositary Shares (ADS), representing an approximately 20.5% ownership interest;

Announced an exclusive development and commercialization agreement with EUSA Pharma (UK) Limited for the orphan biologic products SYLVANT (siltuximab) in Greater China and QARZIBA▼ (dinutuximab beta) in mainland China; and

Announced an exclusive option and license agreement with Leap Therapeutics, Inc. for the clinical development and commercialization of DKN-01, Leap’s anti-Dickkopf-1 (DKK1) antibody, in Asia (excluding Japan), Australia, and New Zealand.
Expected COVID-19 Impact

The Company expects that the worldwide health crisis of COVID-19 will have a negative impact on its operations in China, including commercial sales, regulatory interactions and inspections, and clinical trial recruitment and participation, particularly in the first quarter and possibly longer depending on the scope and duration of the disruption. The Company is working to minimize delays and disruptions and continues to execute on its commercialization, regulatory and clinical development goals in China.
Fourth Quarter and Full Year 2019 Financial Results
Cash, Cash Equivalents, Restricted Cash and Short-Term Investments were $985.50 million as of December 31, 2019, compared to $1.28 billion as of September 30, 2019 and $1.81 billion as of December 31, 2018. Cash and cash equivalents as of December 31, 2019 does not include $2.8 billion of cash received from the sale of ADSs to Amgen in connection with the closing of the Amgen collaboration on January 2, 2020.

Total cash and short-term investments decreased $291.09 million in the fourth quarter of 2019. Cash used in operating activities totaled $267.18 million. Capital expenditures were $15.46 million, and cash used for upfront license payments totaled $20.00 million.

Total cash and short-term investments decreased $823.72 million for the year ended December 31, 2019. Cash used in operating activities totaled $750.27 million. Capital expenditures were $89.61 million, and cash used for upfront license payments totaled $69.00 million.

Revenue for the fourth quarter and year ended December 31, 2019 was $56.89 million and $428.21 million, respectively, compared to $58.67 million and $198.22 million in the same periods in 2018. The slight decrease in total revenue in the quarter compared to the prior year is attributable to the lack of collaboration revenue after the termination of the Celgene collaboration agreement for tislelizumab, offset in part by increased product sales of ABRAXANE, REVLIMID, and VIDAZA in China and the initial sales of BRUKINSA in the United States. The increase in the year-over-year period is primarily due to the $150 million payment in connection with the termination of the tislelizumab collaboration agreement with Celgene Corp., a Bristol-Myers Squibb company (BMS), as well as increased product sales.

Product revenues totaled $56.89 million and $222.60 million for the fourth quarter and year ended December 31, 2019, respectively, compared to $37.76 million and $130.89 million for the same periods in 2018.

Collaboration revenue totaled nil and $205.62 million for the fourth quarter and year ended December 31, 2019, respectively, compared to $20.91 million and $67.34 million for the same periods in 2018. Included in the full year 2019 revenue was the $150 million payment in connection with the termination of the tislelizumab collaboration agreement with Celgene.
Expenses for the fourth quarter and year ended December 31, 2019 were $444.93 million and $1.39 billion, respectively, compared to $339.48 million and $903.99 million in the same periods in 2018.

Cost of Sales for the fourth quarter and year ended December 31, 2019 were $17.98 million and $71.19 million, respectively, compared to $9.19 million and $28.71 million in the same periods in 2018. Cost of sales related primarily to the cost of acquiring ABRAXANE, REVLIMID, and VIDAZA for distribution in China.

R&D Expenses for the fourth quarter and year ended December 31, 2019 were $283.26 million and $927.34 million, respectively, compared to $257.46 million and $679.01 million in the same periods in 2018. The increase in R&D expenses was primarily attributable to increased spending related to ongoing enrollment and expansion of pivotal clinical trials for zanubrutinib and tislelizumab, preparation for additional regulatory submissions of our late-stage drug candidates, manufacturing costs related to pre-commercial activities and supply, as well as increases in spending related to our preclinical-stage programs. Employee share-based compensation expense also contributed to the overall increase in R&D expenses, and was $21.69 million and $76.29 million for the fourth quarter and year ended December 31, 2019, respectively, compared to $16.09 million and $54.38 million for the same periods in 2018, due to increased headcount and a higher share price.

SG&A Expenses for the fourth quarter and year ended December 31, 2019 were $143.35 million and $388.25 million, respectively, compared to $72.49 million and $195.39 million in the same periods in 2018. The increase in SG&A expenses was primarily attributable to increased headcount, including the expansion of our commercial teams to support the distribution of our commercial products in China and in the United States, increased commercial activities as well as higher professional service fees and costs to support our growing operations. The overall increase in SG&A expenses was also attributable to higher SG&A-related share-based compensation expense, which was $16.65 million and $57.86 million for the fourth quarter and year ended December 31, 2019, respectively, compared to $9.87 million and $32.74 million for the same periods in 2018, due to increased headcount and a higher share price.

Net Loss for the fourth quarter and year ended December 31, 2019 was $388.06 million and $948.63 million, or $0.49 and $1.22 per share, or $6.39 and $15.80 per ADS, respectively, compared to $268.26 million and $673.77 million, or $0.35 and $0.93 per share, or $4.52 and $12.15 per ADS, respectively, in the same periods in 2018.

On March 2, 2020 FibroGen, Inc. (NASDAQ: FGEN) reported financial results for the fourth quarter and full year of 2019 and provided an update on the company’s recent developments (Press release, FibroGen, MAR 2, 2020, View Source [SID1234555055]).

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"I am thrilled to be joining FibroGen at such an important inflection point for the company. In 2019 we submitted the roxadustat U.S. New Drug Application (NDA), launched roxadustat in China and Japan, and initiated pivotal programs for pamrevlumab in idiopathic pulmonary fibrosis (IPF) and locally advanced unresectable pancreatic cancer (LAPC)." said Enrique Conterno, Chief Executive Officer, FibroGen. "We begin 2020 with a strong foundation on which to build and with continued commitment to unlocking new treatment options that improve patients’ lives.

FibroGen has a unique opportunity to leverage its world class science in three areas of focus: ensuring the regulatory and commercial success of roxadustat – a potentially transformational oral medicine in anemia therapy, first demonstrated in patients with chronic kidney disease; accelerating the development of pamrevlumab, in the three high-value indications of IPF, LAPC, and Duchenne muscular dystrophy (DMD); and advancing innovation of our hypoxia-inducible factor (HIF) and connective tissue growth factor (CTGF) platforms."

Key Events in Recent Months and Other Developments

Roxadustat

U.S. NDA for roxadustat for the treatment of anemia of chronic kidney disease (CKD), in non-dialysis-dependent and dialysis-dependent patients, accepted with a Prescription Drug User Fee Act (PDUFA) date of December 20, 2020.

Received expanded approval of roxadustat (China tradename: 爱瑞卓) in China for the treatment of anemia in CKD patients who are not dialysis-dependent.

Achieved roxadustat inclusion in the China National Reimbursement Drug List.

In Japan, partner Astellas received approval of and launched roxadustat (Japan trade name Evrenzo) in anemia in dialysis-dependent CKD patients, and submitted the supplemental NDA for the non-dialysis indication this past January.

Results from the open-label portion of our Phase 3 study of roxadustat for treatment of anemia in patients with myelodysplastic syndromes (MDS) presented at the 2019 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. The randomized placebo-controlled, double-blind portion of this global Phase 3 study is ongoing.

Initiated Phase 2 open-label study of roxadustat for chemotherapy-induced anemia (CIA).

Pamrevlumab

Initiated the ZEPHYRUS Phase 3 clinical study of pamrevlumab in patients with idiopathic pulmonary fibrosis (IPF).

In 2020, we will initiate ZEPHYRUS 2, a second IPF Phase 3 study similar in design to ZEPHYRUS.

We plan to enroll approximately 340 patients in each study.

Initiated the LAPIS Phase 3 clinical trial of pamrevlumab for the treatment of patients with locally advanced unresectable pancreatic cancer (LAPC).

Upcoming Events

In Europe, partner Astellas expects to submit Marketing Authorization Application (MAA) for roxadustat for treatment of dialysis- and non-dialysis-dependent CKD anemia in the second quarter of 2020.

Plan to initiate a pamrevlumab Phase 3 study in DMD in the second half 2020.

Corporate and Financial

Net loss for the fourth quarter of 2019 was $98.1 million, or $1.12 net loss per basic and diluted share, compared to a net income of $21.0 million, or $0.25 net income per basic share and $0.23 net income per diluted share one year ago.

Net loss for the year was $77.0 million, or $0.89 net loss per basic and diluted share, compared to a net loss of $86.4 million, or $1.03 net loss per basic and diluted share one year ago.

At December 31, 2019, FibroGen had $627.1 million in cash, restricted time deposits, cash equivalents, investments, and receivables.

Based on our latest forecast, we estimate our 2020 ending cash to be in the range of $720 million to $730 million.

Conference Call and Webcast Details

FibroGen will host a conference call and webcast today, Monday, March 2, 2020, at 5:00 p.m. Eastern Time (2:00 p.m. Pacific Time) to discuss financial results and provide a business update. A live audio webcast of the call may be accessed in the investor section of the company’s website, www.fibrogen.com. To participate in the conference call by telephone, please dial 1 (877) 658-9081 (U.S. and Canada) or 1 (602) 563-8732 (international), reference the FibroGen fourth quarter 2019 financial results conference call, and use confirmation number 8058848. A replay of the webcast will be available shortly after the call for a period of four weeks. To access the replay, please dial 1 (855) 859-2056 (domestic) or 1 (404) 537-3406 (international), and use passcode 8058848.

About Roxadustat

Roxadustat is a first-in-class, orally administered small molecule HIF-PH inhibitor that promotes erythropoiesis through increasing endogenous production of erythropoietin, improving iron regulation, and overcoming the negative impact of inflammation on hemoglobin synthesis and red blood cell production by downregulating hepcidin. Administration of roxadustat has been shown to induce coordinated erythropoiesis, increasing red blood cell count while maintaining plasma erythropoietin levels within or near normal physiologic range in multiple subpopulations of chronic kidney disease (CKD) patients, including in the presence of inflammation and without a need for supplemental intravenous iron. Roxadustat is currently approved in China for the treatment of anemia in CKD patients on dialysis and patients not on dialysis and approved in Japan for the treatment of anemia in CKD patients on dialysis. The NDA filing for roxadustat for the treatment of CKD anemia was accepted by the U.S. Food and Drug Administration in February 2020. Astellas is in the process of preparing an MAA for submission to the European Medicines Agency in the second quarter of 2020. Roxadustat is in Phase 3 clinical development in the U.S. and Europe and in Phase 2/3 development in China for anemia associated with myelodysplastic syndromes (MDS), and in a Phase 2 U.S. trial for treatment of chemotherapy-induced anemia.

Astellas and FibroGen are collaborating on the development and commercialization of roxadustat for the treatment of anemia in territories including Japan, Europe, the Commonwealth of Independent States, the Middle East, and South Africa. AstraZeneca and FibroGen are collaborating on the development and commercialization of roxadustat for the treatment of anemia in the U.S., China, and other markets in the Americas and in Australia/New Zealand as well as Southeast Asia.

About Pamrevlumab

Pamrevlumab is a first-in-class antibody developed by FibroGen to inhibit the activity of connective tissue growth factor (CTGF), a common factor in fibrotic and proliferative disorders characterized by persistent and excessive scarring that can lead to organ dysfunction and failure. Pamrevlumab is in Phase 3 clinical development for the treatment of idiopathic pulmonary fibrosis (IPF) and for the treatment of locally advanced unresectable pancreatic cancer (LAPC), and in Phase 2 clinical development for the treatment of Duchenne muscular dystrophy (DMD). The U.S. Food and Drug Administration has granted Orphan Drug Designation to pamrevlumab for the treatment of patients with IPF, LAPC, and DMD. Pamrevlumab has also received Fast Track designation from the U.S. Food and Drug Administration for the treatment of patients with IPF and LAPC. Across all clinical studies, pamrevlumab has consistently demonstrated a good safety and tolerability profile to date. For information about pamrevlumab studies currently recruiting patients, please visit www.clinicaltrials.gov.

On March 2, 2020 Alpine Immune Sciences, Inc. (NASDAQ:ALPN) reported the cancellation of the Company’s presentation and webcast at the Cowen 40th Annual Healthcare Conference scheduled for Tuesday, March 3, 2020 at 11:20 am. Eastern Time (Press release, Alpine Immune Sciences, MAR 2, 2020, View Source [SID1234555054]). The Company is taking precautionary measures in response to the evolving coronavirus (COVID-19) situation in the Seattle area.

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On March 2, 2020 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported business highlights and financial results for the fourth quarter ended December 31, 2019 (Press release, Fate Therapeutics, MAR 2, 2020, View Source [SID1234555053]).

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"In 2019, we made tremendous progress in pioneering the clinical development of off-the-shelf, iPSC-derived cancer immunotherapy. Our FT500 program demonstrated that multiple doses of iPSC-derived NK cells can be delivered off-the-shelf to a patient in a safe manner without patient matching. Additionally, our FT516 program provided initial clinical evidence that engineered iPSC-derived NK cells may confer anti-tumor activity and deliver clinically meaningful benefit to patients. We also showed the unmatched scalability of our proprietary iPSC product platform, having manufactured hundreds of cryopreserved, infusion-ready doses of our iPSC-derived NK cell product candidates at a low cost per dose in our new GMP manufacturing facility," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "In 2020, we look forward to additional clinical data from our FT500 and FT516 programs, and initial clinical data from FT596, our ground-breaking iPSC-derived CAR NK cell product candidate for the treatment of B-cell malignancies designed to overcome many of the limitations inherent in current CAR T-cell immunotherapies. We also expect to begin clinical investigation of our off-the-shelf, iPSC-derived NK cell programs in multiple myeloma with planned IND submissions for FT538, the first-ever CRISPR-edited, iPSC-derived cell therapy, and for FT576, our multi-antigen targeted, CAR-BCMA product candidate. Finally, under our collaboration with Memorial Sloan Kettering, we strive to be the first group in the world to bring off-the-shelf, iPSC-derived CAR T-cell therapy to patients."

Clinical Programs

Encouraging Safety, Tolerability and Immunogenicity Data from FT500 Phase 1 Study Announced. In December, the Company reported initial clinical data from the dose-escalation stage of the FT500 Phase 1 study for the treatment of advanced solid tumors as of a November 28, 2019 data cutoff (n=8 monotherapy; n=4 in combination with checkpoint inhibitor therapy). The multi-dose treatment course, consisting of three once-weekly doses of FT500 over up to two 30-day cycles, was well-tolerated, and there were no dose-limiting toxicities, no FT500-related Grade ≥3 adverse events (AEs) or serious adverse events (SAEs), and no incidents of cytokine release syndrome, neurotoxicity, or graft-versus-host disease, reported in the 12 patients. Additionally, based on assessments of the patients’ T-cell compartment and antibody repertoire, an adverse immune response against FT500 was not evident over the multi-dose treatment course. The Company has amended the FT500 clinical protocol to include IL-2 administration to support NK cell activity, and is initiating the dose-expansion stage of the FT500 Phase 1 study in patients who are refractory to, or have relapsed following, checkpoint inhibitor therapy at 300 million cells per dose in combination with the checkpoint inhibitor on which the patient failed or progressed.
Initial Patients Treated with FT516, the First-ever Engineered, iPSC-derived Cellular Immunotherapy. In December, the Company announced that the first two patients were treated with FT516, the Company’s off-the-shelf NK cell cancer immunotherapy derived from a clonal master iPSC line engineered to express a novel high-affinity, non-cleavable CD16 (hnCD16) Fc receptor. Each patient received three once-weekly doses of FT516 over a 30-day cycle, and there were no FT516-related Grade ≥3 adverse events (AEs) or serious adverse events (SAEs), and no incidents of cytokine release syndrome, neurotoxicity, or graft-versus-host disease, reported by investigators. Each patient was eligible to receive a second 30-day cycle of three once-weekly doses of FT516. The FT516 study is an open-label, multi-dose Phase 1 clinical trial as a monotherapy for the treatment of AML and in combination with CD20-directed monoclonal antibodies for the treatment of advanced B-cell lymphoma.
FT516 Clinical Investigation Expanded to Solid Tumors. In January, the Company announced that the U.S. Food and Drug Administration (FDA) allowed its second IND application for FT516, enabling clinical investigation of FT516 in combination with PDL1-, PD1-, EGFR- and HER2-targeting monoclonal antibody (mAb) therapies across a broad range of solid tumors. The Company intends to initially evaluate FT516 in combination with avelumab in patients with advanced solid tumors who are refractory to, or have relapsed following, at least one line of anti-PDL1 mAb therapy. The multi-dose treatment course consists of three once-weekly doses of FT516 over up to two 30-day cycles.
Patient Enrollment Initiated in FT596 Phase 1 Study for Advanced B-cell Malignancies. The Company is currently conducting an open-label Phase 1 clinical trial of FT596, the Company’s first off-the-shelf, iPSC-derived chimeric antigen receptor (CAR) NK cell cancer immunotherapy and the first cellular immunotherapy engineered with three active anti-tumor modalities, to be cleared for clinical investigation by the FDA. In addition to a proprietary CAR targeting CD19, FT596 expresses a hnCD16 Fc receptor for coincident targeting of additional tumor-associated antigens expressed on cancer cells, such as CD20, to overcome antigen escape. FT596 also expresses an interleukin-15 receptor fusion (IL-15RF), a potent cytokine complex that promotes survival, proliferation and trans-activation of NK cells and CD8 T cells without the need for systemic cytokine support.
FT596 Clinical Supply Successfully Produced in Newly-launched, In-house GMP Facility. In preparation for Phase 1 initiation, the Company produced over 300 cryopreserved, infusion-ready doses of FT596, at a low cost per dose, in its newly-launched Good Manufacturing Practice (GMP) facility. FT596 met stringent release criteria, and the cryopreserved, infusion-ready doses demonstrate robust cell viability and potency, and exhibit high levels of cell-surface expression of both CAR19 and hnCD16 targeting receptors, upon thaw. The Company’s GMP facility, located in San Diego, California, is custom designed to use clonal master iPSC lines as a renewable cell source for the consistent and scaled manufacture of off-the-shelf NK cell and CAR T-cell products.
Preclinical Pipeline

IND-enabling Data Presented for FT538, the First CRISPR-edited, iPSC-derived Cellular Immunotherapy. At the 2019 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December, the Company presented preclinical data for FT538, the Company’s off-the-shelf NK cell cancer immunotherapy for multiple myeloma. FT538 is derived from a clonal master iPSC line engineered with hnCD16 and IL-15RF, and edited for complete elimination of CD38 expression to mitigate anti-CD38 antibody-mediated fratricide. The Company intends to submit an IND application to the FDA for clinical investigation of FT538 in combination with anti-CD38 mAb therapy in the second quarter of 2020.
FT819 Master Engineered iPSC Bank Generated and Fully Characterized. FT819 is the Company’s first off-the-shelf, iPSC-derived CAR T-cell product candidate, and is derived from a clonal master engineered iPSC line engineered with a novel 1XX CAR targeting CD19 inserted into the T-cell receptor alpha constant (TRAC) locus, and edited for complete elimination of T-cell receptor (TCR) expression. At ASH (Free ASH Whitepaper), scientists from the Company and Memorial Sloan Kettering Cancer Center presented new in vivo preclinical data demonstrating that, in a xenograft model of disseminated lymphoblastic leukemia, FT819 enhanced tumor clearance and extended survival as compared to primary CAR19 T cells. The Company intends to submit an IND application to the FDA for clinical investigation of FT819 in the second quarter of 2020.
Fourth Quarter 2019 Financial Results

Cash & Investment Position: Cash, cash equivalents and investments as of December 31, 2019 were $260.9 million, compared to $201.0 million as of December 31, 2018. The increase was driven primarily by $162.4 million in net cash proceeds received by the Company from its September 2019 public offering of common stock. These proceeds were offset by the Company’s use of cash to fund operating activities and to fully retire its debt facility.
Total Revenue: Revenue was $2.8 million for the fourth quarter of 2019, compared to $1.7 million for the same period in 2018. Revenue for the fourth quarter of 2019 was derived from the Company’s collaboration with Ono Pharmaceutical.
R&D Expenses: Research and development expenses were $25.2 million for the fourth quarter of 2019, compared to $14.1 million for the same period in 2018. The increase in R&D expenses was attributable primarily to an increase in employee compensation, including share-based compensation, and in expenses associated with the clinical development and manufacture of the Company’s product candidates and the conduct of research activities, including under the collaboration with Ono Pharmaceutical.
G&A Expenses: General and administrative expenses were $6.7 million for the fourth quarter of 2019, compared to $4.3 million for the same period in 2018. The increase in G&A expenses was attributable primarily to an increase in employee compensation, including share-based compensation.
Shares Outstanding: Common shares outstanding were 75.7 million as of December 31, 2019 and 64.7 million as of December 31, 2018. Preferred shares outstanding as of December 31, 2019 and December 31, 2018 were 2.8 million, each of which is convertible into five shares of common stock.
Today’s Conference Call and Webcast

The Company will conduct a conference call today, Monday, March 2, 2020 at 5:00 p.m. ET to review financial and operating results for the quarter ended December 31, 2019. In order to participate in the conference call, please dial 877-303-6229 (domestic) or 631-291-4833 (international) and refer to conference ID 9879730. The live webcast can be accessed under "Events & Presentations" in the Investors & Media section of the Company’s website at www.fatetherapeutics.com. The archived webcast will be available on the Company’s website beginning approximately two hours after the event.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with cycles of other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely capable of overcoming numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 300 issued patents and 150 pending patent applications.

About FT500

FT500 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line. The product candidate is being investigated in an open-label, multi-dose Phase 1 clinical trial for the treatment of advanced solid tumors (NCT03841110). The study is designed to assess the safety and tolerability of three once-weekly doses of FT500 as a monotherapy and in combination with one of three FDA-approved immune checkpoint inhibitor (ICI) therapies – nivolumab, pembrolizumab or atezolizumab – in patients that have failed prior ICI therapy. Despite the clinical benefit conferred by approved ICI therapy against a variety of tumor types, these therapies are not curative and, in most cases, patients either fail to respond or their disease progresses on these agents. One common mechanism of resistance to ICI therapy is associated with loss-of-function mutations in genes critical for antigen presentation. A potential strategy to overcome resistance is through the administration of allogeneic NK cells, which have the inherent capability to recognize and directly kill tumor cells with these mutations.

About FT516

FT516 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies. CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. ADCC is dependent on NK cells maintaining stable and effective expression of CD16, which has been shown to undergo considerable down-regulation in cancer patients. In addition, CD16 occurs in two variants, 158V or 158F, that elicit high or low binding affinity, respectively, to the Fc domain of IgG1 antibodies. Numerous clinical studies with FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the 158V variant, which is present in only about 15% of patients, have improved clinical outcomes. FT516 is being investigated in an open-label, multi-dose Phase 1 clinical trial as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-directed monoclonal antibodies for the treatment of advanced B-cell lymphoma (NCT04023071). Additionally, the FDA has allowed investigation of FT516 in an open-label, multi-dose Phase 1 clinical trial in combination with monoclonal antibody therapy, including PDL1-, PD1-, EGFR- and HER2-targeting therapeutic antibodies, across a broad range of solid tumors.

About FT596
FT596 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three anti-tumor functional modalities: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology, which contains a NKG2D transmembrane domain, a 2B4 co-stimulatory domain and a CD3-zeta signaling domain, that targets B-cell antigen CD19; a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; and an IL-15 receptor fusion (IL-15RF) that promotes enhanced NK cell activity. In preclinical studies of FT596, the Company has demonstrated that dual activation of the CAR19 and hnCD16 targeting receptors, in combination with IL-15RF signaling, convey synergistic anti-tumor activity. Increased degranulation and cytokine release were observed upon dual receptor activation in lymphoma cancer cells as compared to activation of each receptor alone, indicating that multi-antigen engagement may elicit a deeper and more durable response. Additionally, in a humanized mouse model of lymphoma, FT596 in combination with the anti-CD20 monoclonal antibody rituximab showed enhanced killing of tumor cells in vivo as compared to rituximab alone. FT596 is being investigated in an open-label Phase 1 clinical trial as a monotherapy, and in combination with rituximab, for the treatment of advanced B-cell lymphoma and in combination with obinutuzumab for the treatment of chronic lymphocytic leukemia (NCT04245722).

On March 2, 2020 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), an oncology-focused pharmaceutical company, reported the commencement of a registered underwritten public offering of $150 million in shares of its common stock (Press release, Karyopharm, MAR 2, 2020, View Source [SID1234555052]). In addition, Karyopharm also intends to grant the underwriters a 30-day option to purchase up to $22.5 million in shares of its common stock.

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J.P. Morgan, Morgan Stanley and Jefferies are acting as joint book-running managers for the offering.

An automatically effective shelf registration statement relating to the shares of common stock offered in the public offering described above was filed with the Securities and Exchange Commission (SEC) on February 26, 2020. The securities may be offered only by means of a written prospectus, including a prospectus supplement, forming a part of the effective registration statement. A preliminary prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. When available, copies of the preliminary prospectus supplement and the accompanying prospectus relating to the offering may also be obtained from J.P. Morgan Securities LLC c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at (866) 803-9204, or by email at [email protected]; Morgan Stanley & Co. LLC, 180 Varick Street, 2nd Floor, New York, NY 10014, Attention: Prospectus Department; or Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, or by email at [email protected], or by phone at (877) 821-7388.

This press release does not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.