On February 27, 2019 Turning Point Therapeutics, Inc., a clinical-stage precision oncology company developing novel drugs that address treatment resistance, reported that it will present preclinical data next month highlighting the potent activity of its kinase inhibitors against targeted oncogene drivers and their mutations (Press release, Turning Point Therapeutics, FEB 27, 2019, View Source [SID1234533755]).

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Four studies were accepted for presentation during poster sessions at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place March 29 to April 3 in Atlanta, including two presentations that further characterize lead clinical asset, repotrectinib, in tumor cells with clinically reported ROS1 and NTRK fusions and their corresponding mutations.

"The pervasive challenge of kinase mutations that lead to treatment resistance has limited the effectiveness of approved and investigational kinase inhibitors," said Athena Countouriotis, M.D., chief executive officer. "Our team has developed a pipeline of novel, small compact kinase inhibitors that have demonstrated early preclinical and clinical effectiveness against targeted gene fusions and their mutations. We are pleased to share several of our preclinical studies at AACR (Free AACR Whitepaper) as we continue to generate clinical evidence for our lead asset repotrectinib in our ongoing Phase 1/2 TRIDENT-1 study."

The preclinical antitumor activities of Turning Point’s TPX-0022, a MET/CSF1R/SRC inhibitor, will be presented for the first time in two poster presentations. TPX-0022 was designed to target not only MET-driven tumor cells by potent inhibition of MET/SRC signaling, but also modulate the tumor microenvironment by inhibition of CSF1R. This dual modulation has demonstrated significant tumor growth inhibition in preclinical models.

The four studies to be presented are:

Title: Repotrectinib, a next generation TRK inhibitor, overcomes TRK resistance mutations including solvent front, gatekeeper and compound mutations
Session: Sunday Mar 31, 2019, 1:00 PM – 5:00 PM
Abstract Number: 4000

Title: Repotrectinib, a new generation ROS1 inhibitor, is highly potent against fusion ROS1s and emerging resistance mutations
Session: Monday April 1, 2019, 8:00 AM – 12:00 PM
Abstract Number: 4832

Title: TPX-0022, a polypharmacology inhibitor of MET/CSF1R/SRC for treatment of cancers with abnormal HGF/MET signaling
Session: Monday April 1, 2019, 8:00 AM – 12:00 PM
Abstract Number: 3719

Title: TPX-0022, a polypharmacology inhibitor of MET/CSF1R/SRC inhibits tumor growth by promoting anti-tumor immune responses
Session: Monday April 1, 2019, 8:00 AM – 12:00 PM
Abstract Number: 3749

Turning Point Therapeutics lead drug candidate, repotrectinib, is being evaluated for the treatment of patients with ROS1+ advanced non-small-cell lung cancer (NSCLC) and patients with ROS1+, NTRK+ or ALK+ advanced solid tumors. A multi-cohort Phase 2 registrational study is planned for the second half of 2019. The company is also developing two multi-targeted kinase inhibitors — TPX-0046, a novel RET/SRC inhibitor, and TPX-0022, a novel MET/CSF1R/SRC inhibitor — and next-generation ALK inhibitors.

About Repotrectinib
Repotrectinib (TPX-0005) is a potent and orally bioavailable investigational small molecule kinase inhibitor of ROS1, TRKs and ALK. The clinical benefits of targeting ROS1, TRK, or ALK fusion kinases have been demonstrated with multiple kinase inhibitors already approved or in clinical studies. The successes of these therapies are often overshadowed by the development of acquired resistance. The acquired solvent front mutations including ROS1 G2032R, TRKA G595R and TRKC G623R, and ALK G1202R render common clinical resistance to the current ROS1, TRK, and ALK inhibitors.

Repotrectinib has demonstrated potency against wildtype and mutated ROS1, TRK and ALK kinases, especially the clinically significant solvent front mutations, gatekeeper mutations, and emerging compound mutations after multiple lines of treatment. Repotrectinib may provide a new opportunity to inhibit the abnormal signaling of ROS1, TRK or ALK in solid malignancies, and overcome multiple resistance mechanisms seen in resistant patients. Repotrectinib is currently being evaluated in a Phase 1/2, open-label, multi-center, first-in-human study of the safety, tolerability, pharmacokinetics and anti-tumor activity in patients with advanced solid tumors harboring ALK, ROS1, or NTRK1-3 rearrangements TRIDENT-1 study (www.clinicaltrial.gov number NCT03093116). Interested patients and physicians can also contact the TP Therapeutics Oncology Clinical Trial Hotline at 1-858-276-0005 or email [email protected].

On February 27, 2019 Bolt Biotherapeutics, Inc., a biotechnology company focused on unleashing the power of the immune system to achieve anti-tumor immunity in patients with its promising Immune-Stimulating Antibody Conjugate (ISAC) platform, reported the forthcoming presentation of preclinical data on its BoltbodyTM technology at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Conference (Press release, Bolt Biotherapeutics, FEB 27, 2019, View Source [SID1234533828]). The conference will be held March 29th through April 3rd in Atlanta, Georgia.

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Details relating to the presentation are as follows:
Abstract Title: TLR7/8 immune-stimulating antibody conjugates elicit robust myeloid activation leading to enhanced effector function and antitumor immunity in pre-clinical models.
Abstract Number: 1559
Date and Time: Monday, April 1, 2019, 8am – 12pm EDT
Session Category: Immunology Session Title: Therapeutic Antibodies
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 25, Poster Board 28

"We are pleased that the first public presentation of our BoltbodyTM technology will occur at the AACR (Free AACR Whitepaper) Annual Meeting," stated David Dornan, Ph.D., senior vice president of research at Bolt Biotherapeutics. "BoltbodyTM ISACs are a new class of therapeutics that harness the ability of toll-like receptor (TLR) agonists to convert cold tumors into immunologically hot tumors following systemic administration. We are rapidly advancing our lead BoltbodyTM therapeutic toward the clinic based upon the promising data."

"It is exciting to share the encouraging data generated by this unique technology which builds upon our growing understanding of the role of myeloid cells in generating effective anti-tumor immunity. Our poster will cover in vitro and in vivo data demonstrating that BoltbodyTM ISACs have the capacity to eliminate tumors in preclinical models," stated Ed Engleman, M.D., Bolt founder and co-director of the Immunology and Immunotherapy Research Program at the Stanford Cancer Institute.

About Bolt Biotherapeutics’ Immune-Stimulating Antibody Conjugate (ISAC) Platform Technology
The Boltbody platform consists of Immune-Stimulating Antibody Conjugates (ISAC) that harness the ability of TLR agonists to convert cold tumors into immunologically hot tumors (illuminating tumors to the immune system allowing them to be invaded by tumor killing cells). BoltbodyTM ISACs have demonstrated the ability to eliminate tumors following systemic administration in preclinical models and have also led to the development of immunologic memory.

On February 27, 2019 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome editing company focused on developing curative therapeutics using CRISPR/Cas9 technology in both in vivo and ex vivo applications, reported operational highlights and financial results for the fourth quarter and year ended December 31, 2018 (Press release, Intellia Therapeutics, FEB 27, 2019, View Source [SID1234533717]). In addition, Intellia highlighted select corporate milestones for 2019 and upcoming events for the first quarter of 2019.

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"We are delivering on our full-spectrum strategy, and we expect to have two candidates in development in 2019. Our in vivo transthyretin amyloidosis program is on track for IND filing in 2020, and by the end of this year we anticipate having our first engineered cell therapy development candidate targeting acute myeloid leukemia," said Intellia President and Chief Executive Officer John Leonard, M.D. "We have shown that a single lipid nanoparticle administration can produce very substantial transthyretin protein reduction in non-human primates, reaching levels that we believe hold great therapeutic promise for patients. We also look forward to sharing additional data on our acute myeloid leukemia program this year. We believe our TCR-based, CRISPR-engineered cell therapy will provide a much-needed option for patients."

Recent Operational Highlights

ATTR Program: During the fourth quarter, Intellia completed confirmatory non-human primate (NHP) studies, previewed in October, using its lead candidate for the treatment of transthyretin amyloidosis (ATTR). Fifty-one days post infusion, these NHP studies verified a favorable tolerability profile across various dose levels, and a near-complete (average of >95 percent) reduction in circulating transthyretin (TTR) protein in the liver. The improvements in TTR protein reduction were the result of certain modifications made to the lipid nanoparticle (LNP) cargo components of the therapy, and these modifications have been incorporated into the ongoing, dose-range finding studies and scale-up activities. These modifications will also have application in subsequent programs. The ATTR program is being co-developed with Regeneron Pharmaceuticals, Inc. (Regeneron) with Intellia being the lead party. Intellia confirmed that it is on track for submitting an Investigational New Drug (IND) application in 2020 for ATTR.
In Vivo Insertion: In October, Intellia demonstrated in vivo CRISPR-mediated, targeted transgene insertion in mouse liver. Data shared at the Annual Congress of the European Society of Gene and Cell Therapy highlighted the use of Intellia’s bi-directional DNA template, delivered in a proprietary hybrid LNP/adeno-associated viral (AAV) template delivery system. Insertion of the human F9 gene, the gene encoding the protein deficient in hemophilia B, yielded Factor IX protein levels in mice at or above therapeutic targets in patients. This work was done in collaboration with Regeneron. Additionally, the Company demonstrated the versatility of the hybrid LNP/AAV approach by successfully inserting a functional human SERPINA1 gene (encoding alpha-1 antitrypsin) into the same locus. These experiments in mice yielded human protein expression levels consistent with those of normal individuals without alpha-1 antitrypsin deficiency.
Engineered Cell Therapies: As part of the broad engineered cell therapy platform that the Company is developing, Intellia and its partner, Ospedale San Raffaele, isolated novel active T cell receptors (TCRs) recognizing an epitope of the Wilms’ Tumor 1 (WT1) protein. This protein is overexpressed in many blood cancers, as well as in solid tumors. T cells modified with these TCRs successfully killed acute myeloid leukemia (AML) blasts in an in vitro model. This work will be the foundation for the Company’s first wholly owned ex vivo development candidate for the treatment of AML.
Novartis: In December, Intellia announced an expansion of the existing cell therapy collaboration with Novartis Institutes for Biomedical Research, Inc. (Novartis) to include ocular stem cells. The Company received a $10 million payment from Novartis in relation to the inclusion of this cell type. Regarding its proprietary LNP delivery system and improvements, Intellia also obtained expanded access to Novartis’ LNP library, including the rights to use these lipids for in vivo or ex vivo applications in any genome editing technology.
Board of Directors: In January of 2019, Intellia appointed Fred Cohen, M.D., D.Phil, F.A.C.P., to its board of directors, adding both biotechnology drug development experience and extensive medical expertise to the current knowledge base of the Company’s board.
Upcoming Milestones

The Company has set forth the following for 2019 pipeline progression:

ATTR: Complete dose-range finding studies, initiate IND-enabling toxicology studies and commence manufacturing of lipid and CRISPR/Cas9 cargo
Engineered Cell Therapy: Nominate first engineered cell therapy development candidate for acute myeloid leukemia by the end of 2019
Present additional in vivo NHP insertion data and ATTR formulation improvement data at upcoming scientific conferences
Upcoming Events

The Company will participate in the following investor events:

Leerink Healthcare Conference, February 28, New York City
Barclays Global Healthcare Conference, March 12, Miami
Fourth Quarter and Full Year 2018 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $314.1 million as of December 31, 2018, compared to $340.7 million as of December 31, 2017. The decrease was driven by cash used to fund operations of approximately $96 million, which was offset in part by $28.5 million of net equity proceeds raised from the Company’s "At the Market" (ATM) agreement, $11.7 million in proceeds from employee-based stock plans, $10.4 million of ATTR cost reimbursements made by Regeneron, and $19.0 million of funding received under the Novartis collaboration. The Novartis funding received included a $10.0 million upfront payment related to the expansion of the existing collaboration in the fourth quarter of 2018.
Collaboration Revenue: Collaboration revenue increased by $1.2 million to $7.9 million during the fourth quarter of 2018, compared to $6.7 million during the fourth quarter of 2017. The increase in collaboration revenue in 2018 was primarily driven by amounts recognized from the expansion of the existing collaboration with Novartis, as well as by amounts recognized under the Company’s ATTR Co/Co agreement with Regeneron. As previously disclosed, Regeneron is obligated to fund approximately 50 percent of the development costs for the ATTR program.
R&D Expenses: Research and development expenses decreased by $1.3 million to $19.9 million during the fourth quarter of 2018, compared to $21.2 million during the fourth quarter of 2017. This decrease was driven primarily by lower consumable costs, as well as the timing of general R&D expenses.
G&A Expenses: General and administrative expenses decreased by $1.5 million to $8.7 million during the fourth quarter of 2018, compared to $10.2 million during the fourth quarter of 2017. This decrease was driven primarily by a decrease in stock-based compensation.
Net Loss: The Company’s net loss was $19.1 million for the fourth quarter of 2018, compared to $24.0 million during the fourth quarter of 2017.

Financial Guidance

Intellia expects that its cash, cash equivalents and marketable securities as of December 31, 2018, as well as technology access and funding from Novartis and Regeneron, will enable Intellia to fund its anticipated operating expenses and capital expenditure requirements into the first half of 2021. This expectation excludes any potential milestone payments or extension fees that could be earned and distributed under the collaboration agreements with Novartis and Regeneron or any strategic use of capital not currently in the base-case planning assumptions.

On February 27, 2019 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte (TIL) technology, reported its fourth quarter and year-end 2018 financial results and provided a corporate update (Press release, Iovance Biotherapeutics, FEB 27, 2019, View Source [SID1234533740]).

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"Over the past year, we took great strides forward in our goal of advancing TIL therapy towards approval in multiple indications and bringing this one-time treatment to patients who have progressed through existing treatment options," commented Maria Fardis, Ph.D., MBA, president and chief executive officer of Iovance Biotherapeutics. "We reported clinical results for our lead program in metastatic melanoma, received acknowledgement from the FDA on a defined path to approval with a single-arm study and have firmly established our optimized, scalable, 22-day manufacturing process. We are well financed to complete the registration-enabling study, Cohort 4, and file the Biologics License Application (BLA) in 2020 for lifileucel. The regenerative medicine advanced therapy (RMAT) designation we received this past year for lifileucel allows for close coordination with the FDA as we move forward. Now that we have demonstrated compelling data in post PD-1 melanoma patients and have received regulatory clarity, we continue our development work in additional indications, such as cervical, while preparing to build internal manufacturing capabilities. Our goals for 2019 will further propel Iovance towards registration and commercialization of TIL therapy."

2018 Highlights

Clinical

·New data from Cohort 2 of lifileucel in the treatment of metastatic melanoma study (C-144-01) was presented in poster and oral presentations at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 33rd Annual Meeting in November 2018. The presentation described results from 47 consecutively dosed, post PD-1 patients with an objective response rate (ORR) of 38%.1 The most common treatment emergent adverse events observed in this cohort include thrombocytopenia, chills, neutropenia, febrile neutropenia and anaemia.
·In the Phase 2 study of LN-145 for cervical carcinoma (C-145-04) preliminary data was reported in October 2018 for 15 patients yielding an ORR of 27%. Patients in the study had a median of five prior therapies. The safety findings from this study remained consistent with previous reports.

Regulatory

·In May 2018, the company was granted orphan drug designation from the U.S. Food and Drug Administration (FDA) for autologous tumor infiltrating lymphocytes for the treatment of cervical cancer with a tumor size of greater than 2 cm in diameter.
·In September 2018, the company received the Regenerative Medicine Advanced Therapy (RMAT) designation from the FDA for lifileucel for the treatment of patients with metastatic melanoma.
·In September 2018, the company held an end of Phase 2 meeting with the FDA during which the agency acknowledged that a single-arm cohort as part of the C-144-01 study can be supportive of initial registration of lifileucel.

Research

·Under a collaboration with Ohio State University, Iovance has developed a product candidate called peripheral blood lymphocytes (PBL). The company anticipates filing an IND for PBL in hematological indications in 2019.

Corporate

·The company completed two underwritten public offerings in 2018 raising approximately $400 million.

2019 Updates

Clinical

·The protocol for the metastatic melanoma study (C-144-01) was amended based on FDA feedback. The trial sites are in process of re-activation for Cohort 4, which is expected to enroll 75 patients. Patient enrollment has commenced.
·The last patient was enrolled in Cohort 2 of the metastatic melanoma study in the fourth quarter of 2018. The company anticipates providing an update on the full cohort of patients at a medical meeting in 2019.
·The protocol for the cervical carcinoma study has been amended to limit the number of prior therapies to no more than three and to exclude patients who have been treated with prior immunotherapy. The company anticipates providing an update on this study at an upcoming medical meeting in 2019.
·The company has dosed over 100 patients with the Gen 2 manufacturing product across multiple studies.

Regulatory

·In February 2019, the company was granted Fast Track designation from the FDA for treatment of patients with recurrent, metastatic, or persistent cervical cancer patients who have progressed while on or after chemotherapy.

Research

·An abstract titled "Persistence of cryopreserved tumor-infiltrating lymphocyte product lifileucel (LN-144) in C-144-01 study of advanced metastatic melanoma" was accepted for presentation at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) meeting March 29-April 3, 2019.

Fourth Quarter 2018 Financial Results

Net loss for the fourth quarter 2018 was $32.6 million, or $0.27 per share, compared to net loss of $25.9 million or $0.36 per share for the fourth quarter 2017.

Research and Development expenses were $27.4 million for the fourth quarter 2018, an increase of $6.7 million compared to $20.7 million for the quarter ended December 31, 2017. The increase in Research and Development expenses is attributable to; an increase in Research and Development staff and the related compensation expense, an increase in clinical trial and manufacturing costs due to the initiation of clinical trials in 2018 for new indications and increased number of patients enrolled across all the studies.

General and administrative expenses were $7.5 million for the fourth quarter 2018, an increase of $2.1 million compared to $5.4 million for the fourth quarter ended 2017. The increase in General and Administrative expenses was primarily attributable to an increase in General and Administrative headcount and related compensation expenses and an increase in external professional service fees.

Full Year 2018 Financial Results

Net loss for the year ended December 31, 2018 was $123.6 million, or $1.27 per share, compared to $92.1 million or $1.41 per share for the year ended December 31, 2017.

Research and Development expenses were $99.8 million for the year ended December 31, 2018, an increase of $28.2 million compared to $71.6 million for 2017. The increase was primarily attributable to an increase in payroll and related expenses, including stock-based compensation expenses, due to a higher number of full-time employees and dedicated consultants as we expanded our internal research efforts and clinical development programs. Further, clinical trial costs increased due to; higher patient enrollment and an increase in the number of clinical sites for lifileucel and LN-145.

General and Administrative expenses were $28.4 million for the year ended December 31, 2018, an increase of $7.1 million compared to $21.3 million for 2017. The increase was primarily attributable to an increase in payroll and related expenses, including stock-based compensation expenses, driven by a higher number of full-time employees and higher stock prices during 2018, and an increase in external professional service fees including preparation and filing of patents.

Cash, Cash Equivalents and Short-term Investments

At December 31, 2018, the company held $468.5 million in cash, cash equivalents and short-term investments, compared to $145.4 million at December 31, 2017. Net cash used in operating activities was $101.2 million during the year ended December 31, 2018.

Iovance anticipates cash, cash equivalents and investments to be between $310 million and $320 million at December 31, 2019.

Webcast and Conference Call

Iovance will host a conference call and live audio webcast to discuss financial results and provide a corporate update today at 4:30 p.m. ET.

To participate in the conference call, please dial 1-844-646-4465 (domestic) or 1-615-247-0257 (international) and reference the access code 7055329. The live webcast can be accessed under "News & Events" in the Investors section of the Company’s website at www.iovance.com, or you may use the link: View Source

A replay of the call will be available from February 27, 2019 at 7:00 p.m. ET to March 6, 2019 at 6:30 p.m. ET. To access the replay, please dial 1-855-859-2056 (domestic) or 1-404-537-3406 (international) and reference the access code 7055329. The archived webcast will be available for thirty days in the Investors section at www.iovance.com.

1 The ORR included one complete response and 17 partial responses, one of which was unconfirmed and pending patient’s subsequent clinical assessment.

On February 27, 2019 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 2018 (Press release, BeiGene, FEB 27, 2019, View Source/phoenix.zhtml?c=254246&" target="_blank" title="View Source/phoenix.zhtml?c=254246&" rel="nofollow">View Source;p=RssLanding&cat=news&id=2389335 [SID1234533788]).

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"Building on a strong foundation, in 2018 we took BeiGene to new heights with our first three new drug applications accepted and currently under priority review in China for zanubrutinib and tislelizumab," said John V. Oyler, Co-Founder, Chief Executive Officer, and Chairman of BeiGene. "In the United States, we received Breakthrough Therapy designation for zanubrutinib in patients with relapsed/refractory mantle cell lymphoma. We have become a global leader in China-inclusive global clinical development, supported by our internal clinical team of more than 800 people and a commitment to high quality standards."

Oyler continued, "In 2019, we plan to continue to grow our commercial business, paving the way for our planned commercial launches in China this year and for our first new drug application in the United States planned for this year or in early 2020."

Recent Business Highlights and Upcoming Milestones

Clinical Programs

Zanubrutinib (BGB-3111), an investigational small molecule inhibitor of Bruton’s tyrosine kinase (BTK) designed to maximize BTK occupancy and minimize off-target effects

Received Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy;
Granted priority review by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA, formerly known as CFDA) to new drug applications (NDAs) for the treatment of patients with relapsed or refractory (R/R) MCL and with R/R chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL);
Presented full results of the pivotal Phase 2 trial in Chinese patients with R/R MCL in an oral presentation at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting;
Presented updated data from a global Phase 1 trial in patients with MCL at the ASH (Free ASH Whitepaper) Annual Meeting;
Completed enrollment of a significantly expanded cohort 2, of 110 previously untreated patients with 17p deletion in the Phase 3 trial in first-line CLL/SLL; and
Initiated a global Phase 2 trial in patients with R/R marginal zone lymphoma (MZL).
Expected Milestones for Zanubrutinib in 2019

Receive approvals in China for the treatment of patients with R/R MCL and R/R CLL/SLL;
Submit an initial NDA for zanubrutinib in the U.S. in 2019 or early 2020;
Announce top-line results from the pivotal Phase 2 trial in Chinese patients with Waldenström macroglobulinemia (WM) and submit an NDA in China for WM;
Announce top-line results from the Phase 3 trial comparing zanubrutinib to ibrutinib in patients with WM; and
Present updated data from the global Phase 1 trial in WM and MCL; pivotal data from the China Phase 2 trials in R/R MCL and CLL/SLL; Phase 1 obinutuzumab combination data in CLL/SLL; data from the MYD88WT cohort of the Phase 3 WM trial; updated data from the Phase 1 obinutuzumab combination trial in non-Hodgkin’s lymphoma (NHL); and updated data from the global Phase 1 trial in CLL/SLL.
Tislelizumab (BGB-A317), an investigational humanized IgG4 anti–PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages

Granted priority review by the CDE of NMPA to our NDA for the treatment of patients with R/R classical Hodgkin’s lymphoma (cHL);
Presented data from the pivotal Phase 2 trial of tislelizumab in Chinese patients with R/R cHL in an oral session at the ASH (Free ASH Whitepaper) Annual Meeting;
Presented updated data from Phase 1 trial expansion cohorts in patients with urothelial carcinoma, esophageal, gastric, hepatocellular, and non-small cell lung cancers at the European Society for Medical Oncology Immuno-Oncology (ESMO-IO) congress;
Presented Phase 2 clinical results in esophageal squamous cell carcinoma (ESCC) and gastric cancer (GC) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO-GI);
Completed enrollment of the global Phase 2 trial in second- or third-line patients with hepatocellular carcinoma (HCC); and
Initiated the following clinical trials:
— A global Phase 3 trial of tislelizumab in combination with chemotherapy in patients with front-line advanced gastric or gastroesophageal junction adenocarcinoma; and
— A global Phase 3 trial of tislelizumab in combination with chemotherapy in patients with front-line, locally advanced recurrent or metastatic ESCC.
Expected Milestones for Tislelizumab in 2019

Receive NDA approval in China for treatment of patients with R/R cHL;
Announce top-line results from the pivotal Phase 2 trial in Chinese and Korean patients with PD-L1 positive urothelial bladder cancer (UBC) and submit an NDA in China for UBC;
Announce top-line results from the global Phase 2 trial in second- or third-line patients with HCC and have regulatory discussions;
Present updated China pivotal Phase 2 data in R/R cHL; updated Phase 2 chemotherapy combination data; and Phase 1 data from China trials;
Complete or close to completing enrollment in all four ongoing Phase 3 trials in lung and liver cancers; and
Initiate additional pivotal solid tumor trials.
Pamiparib (BGB-290), an investigational small molecule PARP inhibitor

Presented preliminary Phase 1/2 trial data of pamiparib in combination with radiation therapy and/or temozolomide in patients with newly diagnosed or R/R glioblastoma in an oral presentation at the 23rd Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology (SNO); and
Initiated a global Phase 2 trial in patients with metastatic castration-resistant prostate cancer (mCRPC) with homologous recombination deficiency (HRD).
Expected Milestones for Pamiparib in 2019

Announce top-line results from the pivotal Phase 2 trial in Chinese patients with previously treated ovarian cancer in late 2019 or early 2020; and
Present data in patients with ovarian cancer from the global Phase 1 trial and updated Phase 1 combination data.
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

Expanded Phase 1 combination trial with tislelizumab in China and Australia to a total of five advanced solid tumors including non-small cell lung cancer, renal cell carcinoma, ovarian cancer, HCC, and GC.
BGB-A425, an investigational TIM-3 antibody

Initiated a global Phase 1 trial in combination with tislelizumab.
Manufacturing

Substantially completed physical construction of the commercial-scale biologics manufacturing facility in Guangzhou, China, with four 2,000 liter KUBio bioreactors installed.
Expected Milestone for Manufacturing in 2019

Complete Phase 1 construction of the Guangzhou manufacturing facility, with expanded capacity to follow, to support the manufacturing of tislelizumab and other potential drug candidates in the pipeline.
Commercial Operations

Generated $37.76 million and $130.89 million in product revenue in the fourth quarter and year ended December 31, 2018, respectively, from sales in China of ABRAXANE, REVLIMID and VIDAZA, which represents a 142% increase and a 436% increase, respectively, compared to the same periods in 2017 (2017 revenue was from the last four months of the year after the Celgene transaction closed on August 31, 2017); and
In support of the planned commercial launch of zanubrutinib in the United States, the Company made key hires in sales and marketing, market access, commercial operations, and business analytics. In China, the Company more than quadrupled the size of its commercial team since September 2017.
Corporate Developments

Announced license and collaboration agreements with Zymeworks Inc., under which BeiGene acquired exclusive development and commercial rights in Asia-Pacific for Zymeworks’ HER2-targeted therapeutic candidates ZW25 and ZW49, and a research and license agreement under which BeiGene acquired rights to internally develop and commercialize globally up to three other bispecific antibodies using Zymeworks’ Azymetric and EFECT platforms; and
Appointed Dr. Yong (Ben) Ben as Chief Medical Officer, Immuno-Oncology. Dr. Ben has extensive experience in immuno-oncology and early- to late-stage drug development, with multiple successful NDAs and biologics license applications (BLAs), including most recently the approval of PD-L1 immunotherapy IMFINZI (durvalumab) for the treatment of certain patients with locally advanced or metastatic urothelial cancer. Prior to joining BeiGene, he served most recently as chief medical officer of BioAtla, and previously worked at other pharmaceutical companies, including AstraZeneca, Millennium Pharmaceuticals, and Pfizer.
Fourth Quarter and Full Year 2018 Financial Results

Cash, Cash Equivalents, Restricted Cash and Short-Term Investments were $1.81 billion as of December 31, 2018, compared to $2.10 billion as of September 30, 2018 and $837.52 million as of December 31, 2017.

The decrease of $291.85 million in the fourth quarter of 2018 was primarily due to $193.89 million of cash used in operating activities, a $60 million upfront payment made to Zymeworks under our collaboration agreement, $23.25 million for investments in property, plant and equipment, and the payment of the remaining $30.35 million acquisition cost for our research, development, and office facility in Changping, Beijing, China.
The increase of $971.71 million from the prior year period was primarily due to net proceeds received from our global follow-on offering and initial listing on the Hong Kong Stock Exchange of $869.71 million in August 2018 and net proceeds from our follow-on offering on the NASDAQ of $757.59 million in January 2018. These net proceeds were partially offset by $547.72 million of cash used in operating activities, $70 million in upfront payments related to the Zymeworks and Mirati collaboration agreements, investments in property, plant and equipment totaling $70.28 million and primarily attributable to the build-out of our Guangzhou biologics manufacturing facility, and $38.30 million of total cost related to the acquisition of our Changping facility.
Revenue for the fourth quarter and year ended December 31, 2018 was $58.67 million and $198.22 million, respectively, compared to $18.17 million and $238.39 million in the same periods in 2017. The increase in the quarter-over-quarter period is attributable to increased product revenue in China and collaboration revenue under our license and collaboration agreements with Celgene. The decrease in the year-over-year period is due to the upfront payment recognized in 2017 under our collaboration agreement with Celgene for tislelizumab.

Product revenue from sales of ABRAXANE, REVLIMID and VIDAZA in China totaled $37.76 million and $130.89 million for the fourth quarter and year ended December 31, 2018, respectively, compared to $15.61 million and $24.43 million for the same periods in 2017 (2017 revenue was from the last four months of the year after the Celgene transaction closed on August 31, 2017).
Collaboration revenue totaled $20.91 million and $67.34 million for the fourth quarter and year ended December 31, 2018, respectively, compared to $2.57 million and $213.96 million for the same periods in 2017.
Expenses for the fourth quarter and year ended December 31, 2018 were $339.48 million and $903.99 million, respectively, compared to $121.97 million and $336.84 million in the same periods in 2017.

Cost of sales for the fourth quarter and year ended December 31, 2018 were $9.19 million and $28.71 million, respectively, compared to $3.03 million and $4.97 million in the same periods in 2017 (the full year period in 2017 included only the last four months of the year after the Celgene deal closed on August 31, 2017). Cost of sales related 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, 2018 were $257.46 million and $679.01 million, respectively, compared to $91.34 million and $269.02 million in the same periods in 2017. The increase in R&D expenses was primarily attributable to increased spending on our ongoing and newly initiated late-stage pivotal clinical trials, preparation for regulatory submissions and commercial launch 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. Also contributing to the fourth quarter and year-over-year increases were expenses for in-process research and development collaborations, which totaled $79 million in the fourth quarter of 2018 (including $60 million related to the Zymeworks collaboration and $19 million related to the termination of the Merck pamiparib collaboration) and $89 million (inclusive of the $10 million related to the Mirati collaboration) for the year ended December 31, 2018. We did not have any in-process research and development expense from collaborations in the fourth quarter or year ended December 31, 2017. Employee share-based compensation expense also contributed to the overall increase in R&D expenses, and was $16.09 million and $54.38 million for the fourth quarter and year ended December 31, 2018, respectively, compared to $10.95 million and $30.61 million for the same periods in 2017, due to increased headcount and a higher share price.
SG&A Expenses for the fourth quarter and year ended December 31, 2018 were $72.49 million and $195.39 million, respectively, compared to $27.42 million and $62.60 million in the same periods in 2017. 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 potential launches of our late-stage drug candidates, 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 $9.87 million and $32.74 million for the fourth quarter and year ended December 31, 2018, respectively, compared to $5.51 million and $12.25 million for the same periods in 2017, due to increased headcount and a higher share price.
Net Loss for the fourth quarter and year ended December 31, 2018 was $268.26 million and $673.77 million, or $0.35 and $0.93 per share, or $4.52 and $12.15 per American Depositary Share (ADS), respectively, compared to $99.32 million and $93.11 million, or $0.17 and $0.17 per share, or $2.19 and $2.23 per ADS, respectively, in the same periods in 2017.
Conference Call and Investor Event

The Company will hold a live webcast and conference call of fourth quarter and full year 2018 financial results, and business updates and expected upcoming milestones, at 6:00 p.m. EST on February 27 (7:00 a.m. HKT on February 28.) The conference call will be conducted in English, and can be accessed by dialing +1 (844) 461-9930 or +1 (478) 219-0535 in the U.S.; +852 3011-4522 in Hong Kong; or +86 400-682-8609 in mainland China. Please dial in five minutes prior to the start time and provide the passcode 8889396.

In addition, the Company will host an investor and analyst event in Hong Kong from 2:30 p.m. to 4:00 p.m. HKT on February 28 (Thursday, February 28, at 1:30 a.m. EST). This event will be conducted primarily in Mandarin Chinese.

Both events will have live webcast and can be accessed by visiting the investor relations section of the BeiGene website at View Source and/or View Source The replay of both events will be available on the BeiGene website approximately two hours following completion of the events and will be archived for three weeks.

[1] The bank loan is attributable to BeiGene Biologics, a joint venture that is 95% owned by BeiGene, Ltd, totaled $40.79 million as of December 31, 2018 and the current portion of long-term debt for a term note secured by our Suzhou manufacturing facility
[2] The shareholder loan is attributable to a RMB900 million convertible note obtained in 2017 from our joint venture partner for the construction and operation of our manufacturing facilities in Guangzhou.

Condensed Consolidated Statements of Operations (U.S. GAAP)
(Amounts in thousands of U.S. dollars, except for shares, American Depositary Shares (ADSs), per share and per ADS data)

[1] Research and development expense for the fourth quarter and year ended December 31, 2018 includes expenses related to in-process research and development collaborations totaling $79 million and $89 million, respectively.