On March 2, 2020 Ziopharm Oncology, Inc. ("Ziopharm" or the "Company") (Nasdaq: ZIOP), reported its financial results for the fourth quarter and year ended December 31, 2019 and provided a corporate update (Press release, Ziopharm, MAR 2, 2020, View Source [SID1234555060]).

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"In the 16 months since forging our corporate independence, we have advanced all our clinical programs, licensed critical intellectual property, recruited key personnel to the Company and Board, and fortified our financial position," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer. "In 2020, we will use this foundation to accelerate our commercial pathway, through enrollment at NCI to TCR-T trial, preparing TCR-T trials with MD Anderson Cancer Center, data readouts on Controlled IL-12 in recurrent GBM and enrollment to trial of CAR-T infused day after gene transfer."

Significant 2019 Achievements

NCI Phase 2 TCR Study. Under the T-cell receptor (TCR) T-cell therapy program, an investigational new drug (IND) application submitted by the National Cancer Institute (NCI) received clearance from the U.S. Food and Drug Administration (FDA) for a phase 2 clinical trial in multiple solid tumors to evaluate use of the Sleeping Beauty platform for TCR-T therapy.

This trial represents a first-in-human non-viral TCR-T trial at NCI

NCI has begun to screen patients for enrollment with patients going through the TCR identification and procurement process; with tumor resection, neoantigen identification, and TCRs made ready for infusion

Study protocol details are available on Clinicaltrials.gov: A Phase 2 Study Using the Administration of Autologous T-Cells Engineered Using the Sleeping Beauty Transposon/Transposase System to Express T-Cell Receptors Reactive Against Mutated Neoantigens in Patients With Metastatic Cancer (NCT0402436)

New MD Anderson Agreement. In October, the Company entered into a lease agreement to expand its R&D footprint and entered into a new Research and Development Agreement with MD Anderson Cancer Center which:

Enables Ziopharm-sponsored clinical studies at MD Anderson based on the Sleeping Beauty non-viral gene transfer platform to generate T cells targeting neoantigens in solid tumors; initially, two approaches will be evaluated infusing autologous T cells expressing

TCRs with specificities for multiple private neoantigens and administering autologous T cells expressing TCRs from a library targeting shared neoantigens in hotspots

Accelerates expansion of the library, licensed from NCI earlier in 2019, of TCRs against neoantigens in hotspots including mutated KRAS, TP53 and EGFR

Phase 2 Combination Study for Controlled IL-12. Under the Controlled IL-12 program, the Company initiated a phase 2 combination trial with Regeneron’s Libtayo to treat patients with recurrent glioblastoma (rGBM).

As prescribed in the study protocol, the Company expects to enroll up to 36 patients at approximately 10 sites. Enrollment is anticipated to be completed in 1H 2020.

This phase 2 trial builds on experience from a phase 1 combination study with another PD-1 inhibitor, OPDIVO, which completed enrollment last year, with additional data expected this year.

Controlled IL-12 Clinical Data. Data publications in 2019 at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and Society for Neuro-Oncology (SNO) annual meetings showed Controlled IL-12, as monotherapy or in combination with a PD-1 inhibitor, resulted in immune-mediated anti-tumor effects in the setting of recurrent GBM. Encouraging results from the phase 1 monotherapy main trial were published in Science Translational Medicine. These publications and presentations are available on Ziopharm’s website.

IND Cleared for CAR-T Study. Under the CAR-T program, an IND was cleared by the FDA for a phase 1 clinical trial to assess CD19-specific CAR-T, produced using Rapid Personalized Manufacturing (RPM).

Up to 24 patients will be enrolled to evaluate infusion of donor-derived RPM CAR-T in patients with CD19+ leukemias and lymphomas who have relapsed after allogeneic bone marrow transplant. This study is being conducted at MD Anderson Cancer Center as an investigator-initiated trial.

The Company also expects partners at Eden BioCell to file an IND for an autologous RPM CD19 trial this year in Taiwan.

Expanded Team and Capabilities. The Company experienced significant growth in 2019, with strategic hires expanding capabilities and increasing staff nearly 50 percent to 73 employees at year end.

Notably, Ziopharm welcomed Sath Shukla, formerly of Vertex Pharmaceuticals, as Chief Financial Officer and Dr. Drew Deniger, who previously worked under Dr. Steven Rosenberg at the NCI, to lead the TCR program.

Chris Bowden, M.D., and Heidi Hagen were appointed as Directors, completing the repopulation of the Board as part of Ziopharm’s reemergence as an independent company.

Strengthened Balance Sheet. Ziopharm completed 2019 with approximately $79.7 million in cash, with another $20.3 million in capital pre-funded at MD Anderson available for the Company’s program.

Subsequent to the close of 2019, the Company raised approximately an additional $98 million through recent financing activities, Ziopharm has dramatically extended its funding horizon and can accelerate the buildout of its TCR program in Houston and the launch of Ziopharm-led TCR clinical trials for patients with solid tumors.

Anticipated Milestones for the First Half of 2020

Sleeping Beauty Cell Therapy Programs

Patient dosing in the NCI-led phase 2 TCR-T trial targeting solid tumors

Initiation of the CD19-specific CAR-T RPM phase 1 trial with membrane bound IL-15 at MD Anderson

Controlled IL-12 Gene Therapy Program

Complete enrollment and initial data readout for phase 2 combination trial with Libtayo

Interim data readout of phase 1 combination trial with OPDIVO

Interim data readout from phase 1 monotherapy trial in expanded cohort

Fourth Quarter 2019 Financial Results

Net loss of the fourth quarter of 2019, was $15.7 million, or $(0.09) per share, compared to net income of $194.5 million, or $1.29 per share, for the fourth quarter of 2018. Net income for the fourth quarter of 2018 reflects the forfeiture and return of all the Company’s Series 1 preferred stock held by a former corporate partner and the relinquishment of Ziopharm’s obligations under a separate agreement, accounting for approximately $207 million.

Research and development expenses were $10.2 million for the fourth quarter of 2019, compared to $8.2 million for the fourth quarter of 2018, primarily reflecting increased clinical trial activity.

General and administrative expenses were $5.8 million for the fourth quarter of 2019, compared to $4.6 million for the fourth quarter of 2018. The increase in general and administrative expenses for the fourth quarter of 2019 is primarily due to increased headcount, growth of intellectual property activity and expanded clinical activity.

The Company ended the fourth quarter 2019 with unrestricted cash resources of approximately $79.7 million.

In addition, a prepayment of approximately $20.3 million remains for work to be conducted by the Company at MD Anderson under the Company’s Research and Development Agreements.

Full Year 2019 Financial Results

Net loss applicable to the common shareholders for the year ended December 31, 2019 was $117.8 million, or $(0.70) per share, basic and diluted, compared to net income applicable to the common shareholders of $137.2 million, or $0.96 per share, basic and diluted, for the year ended December 31, 2018. Net income in 2018 reflects the forfeiture and return of all of the Company’s Series 1 preferred stock held by a former corporate partner and the relinquishment of Ziopharm’s obligations under a separate agreement, accounting for approximately $207 million.

Research and development expenses were $38.3 million for the year ended December 31, 2019, compared to $34.1 million for the year ended December 31, 2018. The increase in research and development expenses for the year ended December 31, 2019 is primarily due to expanded clinical trial activity.

General and administrative expenses were $19.5 million for the year ended December 31, 2019, compared to $19.9 million for the year ended December 31, 2018.

Conference Call and Webcast

Scheduled for today at 4:30 p.m. ET, the conference call can be accessed by dialing 1-844-309-0618 (U.S. and Canada) or 1-661-378-9465 (international). The passcode for the conference call is 6773016. To access the live webcast or the subsequent archived recording, visit the "Investors" section of the Ziopharm website at

www.ziopharm.com. The webcast will be recorded and available for replay on the Company’s website for two weeks.

On March 2, 2020 Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing multifunctional biotherapeutics, reported financial results for the year ended December 31, 2019 (Press release, Zymeworks, MAR 2, 2020, View Source [SID1234555059]).

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"We’ve started the year off strong thanks to significant clinical progress in the second half of 2019 and a recent financing that has provided expanded resources to further advance global development of our clinical candidates, ZW25 and ZW49," said Ali Tehrani, Ph.D., Zymeworks’ President & CEO. "We plan to initiate registration-enabling studies for ZW25 in both biliary tract and gastric cancer, as well as explore additional indications, with a vision toward establishing ZW25 as the new foundational HER2 therapy. We also remain confident in the potential of ZW49 to be transformative in refractory and low HER2-expressing cancers and expect to begin expansion cohorts later this year."

2019 Business Highlights and Recent Developments

Strengthened Balance Sheet

In January 2020, Zymeworks completed an upsized US$320.8 million public financing to accelerate and expand global development of its lead clinical candidates, ZW25 and ZW49, and support further advancement of its novel preclinical programs.

Robust ZW25 Clinical Data and Initiation of Two Phase 2 Clinical Trials Pave the Way for Upcoming Registration-Enabling Studies

ZW25 has been well tolerated and has demonstrated promising anti-tumor activity both as a single agent and in combination with chemotherapy, supporting the planned initiation of two registration-enabling trials in refractory HER2-positive biliary tract cancer and first-line HER2-positive gastroesophageal adenocarcinomas. In addition, Zymeworks recently initiated a Phase 2 trial and collaboration with Pfizer to evaluate ZW25 in combination with palbociclib and fulvestrant in HER2-positive, hormone receptor-positive breast cancer.

ZW49 Advancing Phase 1 Dose-Escalation and Interim Clinical Update

Zymeworks’ second product candidate, ZW49, began a Phase 1 clinical trial to evaluate safety and anti-tumor activity, and to establish a recommended dose and schedule for expansion cohorts. A recent update highlighted that there had been no dose-limiting toxicities observed and the maximum tolerated dose had not been reached. The majority of treatment-related adverse events were grade 1 or 2, and were reversible and manageable on an outpatient basis. Preliminary results from these initial dose cohorts included anti-tumor activity.

Partner Programs Progress into the Clinic

In 2019, Eli Lilly entered the clinic with a novel bispecific; Merck, Celgene (now BMS), and Daiichi Sankyo advanced bispecific candidates toward clinical testing; GSK expanded its Azymetric partnership; and the first ZymeLink ADC collaboration was signed with Iconic Therapeutics. Zymeworks currently has nine active collaborations that offer up to US$7.9 billion in potential milestone payments as well as royalties on potential product sales.

Financial Results for the Year Ended December 31, 2019

Revenue in 2019 was $29.5 million as compared to $53.0 million in 2018. Revenue for both years was primarily comprised of non-recurring upfront fees, expansion payments and milestone payments from Zymeworks’ licensing and collaboration agreements. Revenue for 2019 included $8.0 million received from Eli Lilly for achievement of a development milestone upon their submission of an IND application, $7.5 million received upon BMS’s exercise of its commercial license option, $3.5 million received upon Daiichi Sankyo’s exercise of a commercial license option, and $7.0 million received in other development milestones and research support and other payments from our partners. Revenue in 2019 also included recognition of $3.5 million from deferred revenue relating to the upfront payment received in the prior year from BeiGene under the 2018 licensing and collaboration agreement for development of ZW25.

Revenue for 2018 included recognition of $23.5 million of the $60.0 million upfront fee from BeiGene associated with a new licensing agreement, an $18.0 million upfront fee related to a second licensing agreement with Daiichi Sankyo, a $5.0 million upfront fee related to a new licensing agreement with LEO Pharma, a $4.0 million research program expansion fee from BMS and $2.5 million in other milestones and research support payments from our partners.

For the year ended December 31, 2019, research and development expenses were $115.9 million as compared to $56.9 million in the prior year. The change was primarily due to an increase in activities related to the progression and expansion of ZW25 clinical studies and the associated manufacturing costs, as well as development activities for ZW49 in 2019, and an increase in other research and development activities, which include an increase in salaries and benefits expense as a result of an increase in headcount and non-cash stock-based compensation expense compared to the same period in 2018. Research and development expense included non-cash stock-based compensation expense of $14.3 million, including expense of $8.4 million related to the mark-to-market revaluation of certain historical liability classified equity awards.

For the year ended December 31, 2019, general and administrative expenses were $64.2 million as compared to $29.5 million in the prior year. The change was due to an increase in headcount to support our expanding research and development activities and non-cash stock-based compensation expense. General and administrative expense included non-cash stock-based compensation expense of $34.2 million including $27.5 million expense related to the mark-to-market revaluation of certain historical liability classified equity awards.

Net loss for the year ended December 31, 2019 was $145.4 million as compared to $36.6 million in 2018. This increase in net loss was primarily due to the variances in revenue, research and development expenses and general and administration expenses noted above.

Zymeworks expects research and development expenditures to increase over time due to the ongoing development of our product candidates and other clinical, preclinical, and regulatory activities. Additionally, Zymeworks anticipates continuing to receive revenue from its existing and future strategic partnerships, including technology access fees, milestones and research support payments. However, Zymeworks’ ability to receive these payments is dependent upon either Zymeworks or its collaborators successfully completing specified research and development activities.

As of December 31, 2019, Zymeworks had $298.9 million in cash and cash equivalents and short-term investments.

On March 2, 2020 PTC Therapeutics, Inc. (NASDAQ: PTCT) reported a corporate update and reported financial results for the fourth quarter and full year ending December 31, 2019 (Press release, PTC Therapeutics, MAR 2, 2020, View Source [SID1234555058]).

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"2019 was a year of outstanding execution for PTC. I’m proud of the progress made in every area of the business," said Stuart Peltz, Ph.D., CEO of PTC Therapeutics. "We’ve significantly expanded our rare disease portfolio, strengthened our global commercial engine and added vital gene therapy manufacturing capabilities, all while delivering on our revenue guidance. The innovation in our diverse, multiplatform pipeline continues to create value for stakeholders."

Key Fourth Quarter and Other Corporate Highlights:

Expanding commercial footprint including continued revenue growth

Total revenue for the full year 2019 was $307 million. The Duchenne muscular dystrophy (DMD) franchise, consisting of Translarna (ataluren) and Emflaza (deflazacort), continues to grow with 2019 revenue of $291 million.

PTC continues to leverage its strong Latin American infrastructure to support the launch of multiple products. In 2019, Translarna received approval from the Brazilian health regulatory authority (ANVISA) for ambulatory nmDMD patients 5 years and older. In addition, Tegsedi (inotersen) received ANVISA approval for the treatment of stage 1 or 2 polyneuropathy in adult patients with hereditary transthyretin amyloidosis (hATTR). In 2019, PTC established an early access program for patients with Familial Chylomicronemia Syndrome (FCS) in Latin America. PTC anticipates filing for approval of Waylivra (volanesorsen) for the treatment of FCS from ANVISA in 2H 2020.

Real-world data from the Translarna STRIDE registry demonstrated that boys with nonsense mutation Duchenne muscular dystrophy (nmDMD) treated with Translarna and standard of care, preserved the ability to walk for 3.5 years longer than compared with those in a matched natural history cohort. Importantly, pulmonary function was also preserved in those treated with Translarna.

A recent publication on Emflaza adds to the growing body of evidence showing its relative benefit and supports the advantage of switching from prednisone to Emflaza. The data in the publication demonstrated that patients treated with Emflaza had better ambulatory function and were able to walk longer, had a lower risk of scoliosis, greater percentage lean body mass and lower weight than patients treated with prednisone.

Positive pivotal trials for risdiplam support planned global launch in broad range of SMA patient types

Following the U.S. Food and Drug Association’s (FDA) acceptance of the New Drug Application (NDA) for risdiplam, a Prescription Drug User Fee Act (PDUFA) date for risdiplam has been set for May 24, 2020.

Roche’s Marketing Authorization Application (MAA) filing with the European Medicines Agency (EMA) for risdiplam is expected mid-year 2020.

Data from part 2 of the FIREFISH trial will be presented during the American Academy of Neurology (AAN) 2020 Annual Meeting, from April 25 to May 1, 2020.

PTC gene therapy platform continues to make progress with regulatory filings and long-term lease of manufacturing facility

In January 2020, the EMA accepted the MAA for the potential approval of PTC-AADC for the treatment of Aromatic l-amino acid decarboxylase (AADC) deficiency. PTC expects the Committee for Medicinal Products for Human Use (CHMP) opinion by year end 2020.

PTC expects to submit a Biologics License Application (BLA) to the FDA in 2Q 2020.

PTC continues to anticipate that more than 300 global, addressable AADC patients will be identified by launch.

In 2019, PTC leased a state-of-the-art biologics manufacturing facility with supporting research and operations buildings in N.J. PTC expects manufacturing at this facility to begin in 2020.

Continued progress with PTC’s multi-platform, multi-product pipeline

The Phase 2 STAR trial in patients with nonsense mutation aniridia evaluating the effect of ataluren did not meet its primary endpoint of Maximum Reading Speed as measured by MNREAD. The results did show a trend in favor of ataluren and the results will be discussed with experts in the coming weeks, after which a decision will be made on a path forward for the program in this indication.

Topline data from the U.S. study to assess dystrophin levels in subjects with nmDMD after treatment with ataluren are expected in 2Q 2020.

In 2019, PTC declared a development candidate in its Huntington’s Disease program. The compound is currently in GLP safety toxicology studies and PTC expects to initiate a clinical trial by the end of the year. The Huntington’s Disease program was developed through PTC’s alternative splicing platform.

In 2020, PTC plans to initiate three clinical trials in two compounds that regulate inflammation and oxidative stress from its Bio-e (redox) platform. PTC acquired the Bio-e platform through an acquisition of assets from BioElectron Technology Corporation in 2019.

Potential registrational trial of PTC743 in patients with Mitochondrial Epilepsy (MEDS) expected to begin in 2Q 2020. MEDS is estimated to affect 5,000-6,000 patients in the U.S. and E.U. combined.

Potential registrational trial of PTC743 in patients with Friedreich Ataxia (FA) expected to begin in 3Q 2020. This is anticipated to be complementary to PTC-FA, a gene therapy candidate for the treatment of FA, which is expected to enter the clinic in 3Q 2020. FA is estimated to affect 25,000 patients worldwide.

PTC857 will enter into a Phase 1 healthy volunteer study in 3Q 2020. The first indication for PTC857 is planned to be GBA Parkinson’s disease based on strong pre-clinical rationale. This condition affects approximately 50,000-90,000 patients in the U.S.

Additional updates on PTC’s platforms and pipeline will be provided at PTC’s Analyst Day on June 16, 2020.

Fourth Quarter and Full-year 2019 Financial Highlights:

Total revenues were $96.5 million for the fourth quarter of 2019, compared to $86.3 million for the fourth quarter of 2018. Total revenues were $307 million for the full year 2019, compared to $264.7 million for the full year 2018.

Translarna net product revenues were $48.4 million for the fourth quarter of 2019, compared to $56 million for the fourth quarter of 2018. Translarna net product revenues were $190 million for the full year 2019, compared to $171 million for the full year 2018.

Emflaza net product revenues were $32.7 million for the fourth quarter of 2019, compared to $29.8 million for the fourth quarter of 2018. Emflaza net product revenues were $101 million for the full year 2019, compared to $92 million for the full year 2018.

GAAP R&D expenses were $81.8 million for the fourth quarter of 2019, compared to $53.6 million for the fourth quarter of 2018. GAAP R&D expenses were $257.4 million for the full year 2019, compared to $172 million for the full year 2018. The increase in R&D expenses reflects costs associated with advancing the gene therapy platform, increased investment in research programs, advancement of the clinical pipeline and the upfront $10M payment for the acquisition of the BioElectron assets.

Non-GAAP R&D expenses were $76.2 million for the fourth quarter of 2019, excluding $5.6 million in non-cash, stock-based compensation expense, compared to $49.7 million for the fourth quarter of 2018, excluding $4 million in non-cash, stock-based compensation expense. Non-GAAP R&D expenses were $236.6 million for the full year 2019, excluding $20.8 million in non-cash, stock-based compensation expense, compared to $155.9 million for the full year 2018, excluding $16.1 million in non-cash, stock-based compensation expense.

GAAP SG&A expenses were $63.5 million for the fourth quarter of 2019, compared to $48.7 million for the fourth quarter of 2018. GAAP SG&A expenses were $202.5 million for the full year 2019, compared to $153.6 million for the full year 2018. The increase in SG&A expenses was primarily due to continued investment to support our commercial activities.

Non-GAAP SG&A expenses were $57.7 million for the fourth quarter of 2019, excluding $5.8 million in non-cash, stock-based compensation expense, compared to $44.2 million for the fourth quarter of 2018, excluding $4.5 million in non-cash, stock-based compensation expense. Non-GAAP SG&A expenses were $181.2 million for the full year 2019, excluding $21.3 million in non-cash, stock-based compensation expense, compared to $136.4 million for the full year 2018, excluding $17.2 million in non-cash, stock-based compensation expense.

Change in the fair value of deferred and contingent consideration was $12.4 million for the quarter ended December 31, 2019, compared to $19.3 million for the quarter ended December 31, 2018. Change in the fair value of deferred and contingent consideration was $48.4 million for the year ended December 31, 2019, compared to $19.3 million for the year ended December 31, 2018. The change is related to the fair valuation of the potential future consideration to be paid to former equity holders of Agilis, as a result of our merger with Agilis which closed in August 2018. Changes in the fair value were due to the re-calculation of discounted cash flows for the passage of time and changes to certain other estimated assumptions.

Net loss was $77.7 million for the fourth quarter of 2019, compared to net loss of $48.3 million for the fourth quarter of 2018. Net loss was $251.6 million for the full year 2019, compared to net loss of $128.1 million for the full year 2018.

Cash, cash equivalents, and marketable securities was $686.6 million at December 31, 2019, compared to $227.6 million at December 31, 2018.

Shares issued and outstanding as of December 31, 2019 were 61,935,870.

PTC Reaffirms Full Year 2020 Guidance as Follows

PTC anticipates full year DMD franchise net product revenues to be between $320 and $340 million.

PTC anticipates GAAP R&D and SG&A expense for the full year 2020 to be between $610 and $640 million.

PTC anticipates Non-GAAP R&D and SG&A expense for the full year 2020 to be between $545 and $575 million, excluding estimated non-cash, stock-based compensation expense of approximately $65 million.

Today’s Conference Call and Webcast Reminder:
Today’s conference call will take place at 4:30 pm ET and can be accessed by dialing (877) 303-9216 (domestic) or (973) 935-8152 (international) five minutes prior to the start of the call and providing the passcode 1732477. A live, listen-only webcast of the conference call can be accessed on the investor relations section of the PTC website at www.ptcbio.com. The accompanying slide presentation will be posted on the investor relations section of the PTC website. A webcast replay of the call will be available approximately two hours after completion of the call and will be archived on the company’s website for 30 days following the call.

On March 2, 2020 Omeros Corporation (Nasdaq: OMER), a commercial-stage biopharmaceutical company committed to discovering, developing and commercializing small-molecule and protein therapeutics for large-market as well as orphan indications targeting inflammation, complement-mediated diseases, disorders of the central nervous system and immune-related diseases, including cancers, reported recent highlights and developments as well as financial results for the fourth quarter and year ended December 31, 2019, which include (Press release, Omeros, MAR 2, 2020, View Source [SID1234555057]):

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4Q 2019 OMIDRIA revenues were $33.4 million, Omeros’ highest revenue quarter to date and representing another quarter of double-digit growth of 12 percent compared to 3Q 2019.

Full year 2019 OMIDRIA revenues were $111.8 million, a 274 percent increase from the prior year.

Net loss in 4Q 2019 was $29.2 million, or $0.58 per share. Net loss for the full year 2019 was $84.5 million, or $1.71 per share. Non-cash expenses for the fourth quarter and the full year of 2019 were $6.3 million, or $0.12 per share, and $24.8 million, or $0.50 per share, respectively. Included in both 4Q and full year net loss is $12.6 million, or $0.25 per share, in connection with Omeros’ election to accelerate the manufacturing schedule for a one-time set of five narsoplimab process validation and commercial lots. These lots were successfully manufactured, provide data to satisfy the BLA process validation requirements, and can be used for commercial sales following approval.

At December 31, 2019, the company had cash, cash equivalents and short-term investments available for operations of $60.8 million.

Data from the narsoplimab pivotal registration trial met the FDA-agreed primary efficacy endpoint, with complete response rates of 54 percent (p<0.0001) in all patients receiving at least one dose of narsoplimab and 65 percent (p<0.0001) in all patients receiving at least the protocol-specified four weeks of dosing, well surpassing the FDA-agreed threshold for efficacy of 15 percent

On the secondary endpoint of 100-day survival, 68 percent of all patients receiving at least one dose of narsoplimab achieved 100-day survival, with 83 percent of patients receiving at least the protocol-specified four weeks of dosing and 93 percent of responders achieving the endpoint. Experts familiar with the pivotal trial data would expect a 100-day survival rate of less than 20 percent in this population.

"2019 was a year of tremendous accomplishment for Omeros," stated Gregory A. Demopulos, M.D., Omeros’ chairman and chief executive officer. "Our pivotal trial in HSCT-TMA generated data that substantially surpass FDA’s agreed threshold for efficacy and enabled submission of the first sections of our rolling BLA, OMIDRIA delivered record annual sales of $112 million, and we discovered a cancer immunity axis controlled by GPR174, a target that we control and expect could change the immuno-oncology landscape. And 2020 is shaping up to be an even better year. We are on track to complete submission of the narsoplimab BLA for HSCT-TMA and look forward to FDA’s review and approval as we move the drug toward two additional indications in IgA nephropathy and aHUS. We expect that 2020 will also bring continued growth in OMIDRIA sales, further clinical development of our OMS527 addiction program, a Phase 1 trial for our MASP-3 inhibitor OMS906, and ongoing progress with our MASP-2 small-molecule inhibitor and next-generation antibody as well as our GPR174 antagonists, driving them toward the clinic. We’ve built a top-tier group of first-in-kind

assets, are delivering on their promise, and expect that they will significantly improve the lives of patients and their families."

Fourth Quarter and Recent Developments

Recent developments regarding narsoplimab, Omeros’ lead human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2) in Phase 3 clinical programs for the treatment of hematopoietic stem-cell transplant-associated thrombotic microangiopathy (HSCT-TMA), Immunoglobulin A (IgA) nephropathy, and atypical hemolytic uremic syndrome (aHUS), include the following:

Omeros recently announced positive data across primary and secondary endpoints in its pivotal trial of narsoplimab in HSCT-TMA patients.

The primary endpoint is a set of rigorous response criteria requiring improvements in HSCT-TMA laboratory markers and improvement in clinical status. The FDA-agreed threshold for the efficacy primary endpoint in the very sick patient population treated in this trial is a response rate of 15 percent. Across all patients receiving at least one dose of narsoplimab, 54 percent (p<0.0001) were complete responders; in patients receiving at least the protocol-specified four weeks of narsoplimab treatment, the complete response rate was 65 percent (p<0.0001).

The secondary endpoints include survival rates and change from baseline in laboratory markers. The 100-day survival rate was 68 percent in all patients who received at least one dose of narsoplimab, 83 percent in patients who received at least the protocol-specified 4 weeks of narsoplimab treatment, and 93 percent in responders. Experts familiar with the pivotal trial data would expect a 100-day survival rate of less than 20 percent in this population. Across all patients, statistically significant improvement was seen in platelet count and LDH and haptoglobin levels (p<0.01 for each marker).

The most commonly reported adverse events in the trial were diarrhea, nausea, vomiting, hypokalemia, neutropenia and fever – all common in stem-cell transplant patients. Six deaths also occurred during the trial and were due to sepsis, progression of the underlying disease and graft-versus-host disease. All of these are common causes of death in this patient population.

In February 2020, Omeros met with FDA to discuss the chemistry, manufacturing and controls aspects of the Biologics License Application (BLA) for narsoplimab in HSCT-TMA. At the meeting, FDA requested near-term manufacturing dates for narsoplimab so that FDA’s pre-approval inspections could be scheduled. FDA and Omeros also reached agreement on requirements for stability data and release assays for the BLA

Data from the narsoplimab pivotal trial in HSCT-TMA were presented and discussed by a panel of international experts in hematopoietic stem-cell transplantation at a recent continuing medical education symposium held at the Transplant and Cellular Therapy Conference in Orlando.

Omeros initiated a collaboration with myTomorrows, a global health technology company, to broaden its expanded access program to support international availability of narsoplimab to eligible patients who have no other treatment options.

The ARTEMIS-IGAN Phase 3 clinical trial for narsoplimab in IgA nephropathy is ongoing at 91 sites in the U.S. and internationally, with additional sites coming on line. Data readout is expected next year.

Multiple manuscripts directed to narsoplimab in IgA nephropathy have been accepted for publication or are under review by peer-reviewed journals. Most recently, a review article entitled "MASP-2 Inhibition as Potential Strategy for IgA Nephropathy Management" authored by Drs. Jonathan Barratt of University of Leicester and Richard Lafayette of Stanford University was accepted for publication in the journal Drugs of the Future.

Recent developments regarding OMIDRIA include the following:

The Non-Opioids Prevent Addiction in the Nation (NOPAIN) Act was introduced in the both the U.S. House of Representatives and the U.S. Senate during the fourth quarter. The proposed legislation has strong bipartisan backing in both chambers of Congress and is supported by a diverse group of grassroots organizations. If passed, the legislation would mandate separate payment by Centers for Medicare and Medicaid Services (CMS) for a period of five years for non-opioid pain treatments used during surgery, like OMIDRIA.

The new product-specific permanent J-code for OMIDRIA became effective on October 1, 2019. J-codes standardize the submission and payment of insurance claims across Medicare, Medicare Advantage, Medicaid and commercial insurance plans.

Updates regarding Omeros’ other development programs and platforms include the following:

Omeros’ MASP-3 inhibitor OMS906 is on track for clinical entry in June of this year. Initially targeting paroxysmal nocturnal hemoglobinuria (PNH), OMS906 is expected to allow monthly subcutaneous dosing.

Following positive results from the Phase 1 study, Omeros is planning for a Phase 2 trial of its phosphodiesterase 7 inhibitor OMS527 in nicotine addiction.

In the fourth quarter of 2019, Omeros presented new data on its GPR174 immuno-oncology program at international medical congresses. Data from human ex vivo studies demonstrate that GPR174 inhibition results in downregulation of checkpoint and tumor-promoting factors. In addition, data from animal models reveal enhanced anti-tumor immune responses in GPR174-deficient mice and synergism between adenosine receptor antagonists and GPR174 antagonists in promoting interleukin-2 (IL-2) and interferon-γ (IFN-γ) production from human T cells. Omeros discovered a cancer-immunity axis controlled by GPR174 and is building an exclusive intellectual property position directed to modulation of GPR174 for the treatment of cancer.

In December 2019, Omeros raised $54.2 million in net proceeds in an underwritten offering of common stock.

Financial Results

Fourth Quarter 2019

For the quarter ended December 31, 2019, revenues were $33.4 million, all relating to sales of OMIDRIA. This compares to OMIDRIA revenue of $22.0 million for the same period in 2018. On a sequential quarter-over-quarter basis, OMIDRIA revenue increased by $3.6 million or 12 percent. The increases from the prior year and from the prior quarter are primarily due to a growing number of purchasing accounts as well as deeper penetration within accounts across hospitals, ambulatory surgery centers and government payers.

Total operating costs and expenses for the quarter ended December 31, 2019 were $57.1 million compared to $40.5 million for the comparable period in 2018 and $41.0 million in the preceding quarter. The increase in both cases primarily reflects $12.6 million of expenses incurred ahead of schedule due to Omeros’ election to accelerate the manufacturing schedule for a one-time set of five narsoplimab process validation and commercial lots. These lots were successfully manufactured, provide data to satisfy the BLA process validation requirements, and can be used for commercial sales following approval.

For the three months ended December 31, 2019, Omeros reported a net loss of $29.2 million or $0.58 per share, which included non-cash expenses of $6.3 million ($0.12 per share) and the aforementioned manufacturing expenses of $12.6

million ($0.25 per share). This compares to the prior year’s fourth quarter when Omeros reported a net loss of $23.5 million, or $0.48 per share, which included non-cash expenses of $4.9 million ($0.10 per share).

Full Year 2019

Revenues for the full year 2019 were $111.8 million compared to $29.9 million for full year 2018. The significant increase year-over-year is primarily due to the status of pass-through reimbursement. During the period January 1, 2018 to September 30, 2018, OMIDRIA was not reimbursed separately under Medicare Part B. This had a significant negative impact on revenues during 2018. Following reinstatement of pass-through reimbursement on October 1, 2018, OMIDRIA revenues quickly returned to and exceeded previous levels.

For the year ending December 31, 2019, total costs and expenses were $175.2 million compared to $142.1 million in the prior year. The increase for the current year compared to the prior year is due primarily to the additional narsoplimab manufacturing, an increase in spending on preclinical research and development in our OMS906 program and the resumption of OMIDRIA marketing activities following reinstatement of pass-through reimbursement on October 1, 2018.

At December 31, 2019, the company had cash, cash equivalents and short-term investments available for operations of $60.8 million and an accounts receivable balance of $35.2 million. The company also has an accounts receivable-based line of credit which permits borrowing up to the lesser of $50.0 million and 85 percent of eligible accounts receivable, subject to applicable reserves. We have not borrowed under this facility.

Conference Call Details

Omeros’ management will host a conference call to discuss the financial results and to provide an update on business activities. The call will be held today at 4:30 p.m. Pacific Time; 1:30 p.m. Eastern Time. To access the live conference call via phone, please dial (844) 831-4029 from the United States and Canada or (920) 663-6278 internationally. The participant passcode is 4870947. Please dial in approximately 10 minutes prior to the start of the call. A telephone replay will be available for one week following the call and may be accessed by dialing (855) 859-2056 from the United States and Canada or (404) 537-3406 internationally. The replay passcode is 4870947.

To access the live or subsequently archived webcast of the conference call on the internet, go to the company’s website at www.omeros.com and select "Events" under the Investors section of the website. To access the live webcast, please connect to the website at least 15 minutes prior to the call to allow for any software download that may be necessary.

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.