On February 13, 2020 Bristol-Myers Squibb Company (NYSE: BMY) reported that the U.S. Food and Drug Administration (FDA) has accepted for Priority Review its Biologics License Application (BLA) for lisocabtagene maraleucel (liso-cel), the company’s autologous anti-CD19 chimeric antigen receptor (CAR) T-cell immunotherapy with a defined composition of purified CD8+ and CD4+ CAR T cells for the treatment of adult patients with relapsed or refractory (R/R) large B-cell lymphoma after at least two prior therapies (Press release, Bristol-Myers Squibb, FEB 13, 2020, View Source [SID1234554259]). The FDA has set a Prescription Drug User Fee Act (PDUFA) goal date of August 17, 2020.

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"There remains a critical need for additional therapies in large B-cell lymphoma, particularly for relapsed or refractory patients," said Stanley Frankel, M.D., senior vice president, Cellular Therapy Development, Bristol-Myers Squibb. "Based on the TRANSCEND NHL 001 data, liso-cel has the potential to expand treatment options for those affected by this aggressive blood cancer who did not respond to initial therapies or whose disease has relapsed. This BLA acceptance and Priority Review designation is an important step as we work to improve treatment for these patients in need."

The BLA, submitted by Juno Therapeutics, a wholly owned subsidiary of Bristol-Myers Squibb Company, is based on the safety and efficacy results from the TRANSCEND NHL 001 trial, evaluating liso-cel in 268 patients with R/R large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL), high-grade lymphoma, primary mediastinal B-cell lymphoma and Grade 3B follicular lymphoma. TRANSCEND NHL 001 is the largest study of CD19-directed CAR T cells to support a BLA to date and was recently the subject of an oral presentation at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition.

According to the FDA, a Priority Review designation will direct overall attention and resources to the evaluation of applications for drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications.

Liso-cel was previously granted Breakthrough Therapy and Regenerative Medicine Advanced Therapy designations by the FDA for R/R aggressive large B-cell non-Hodgkin lymphoma, including DLBCL, not otherwise specified (de novo or transformed from indolent lymphoma), PMBCL or Grade 3B FL, and Priority Medicines (PRIME) scheme by the European Medicines Agency for R/R DLBCL.

Liso-cel is an investigational compound that is not approved for use in any country.

About Large B-cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common of large B-cell lymphomas. It is an aggressive form of non-Hodgkin lymphoma (NHL), accounting for three out of every five cases. Approximately one-third of patients with DLBCL relapse after receiving first-line treatment, and about 10% have refractory disease. Historically, median life expectancy for patients who relapse or are refractory to current standard of care treatments is approximately six months.

Bristol-Myers Squibb: Advancing Cancer Research

At Bristol-Myers Squibb, patients are at the center of everything we do. The goal of our cancer research is to increase quality, long-term survival and make cure a possibility. We harness our deep scientific experience, cutting-edge technologies and discovery platforms to discover, develop and deliver novel treatments for patients.

Building upon our transformative work and legacy in hematology and Immuno-Oncology that has changed survival expectations for many cancers, our researchers are advancing a deep and diverse pipeline across multiple modalities. In the field of immune cell therapy, this includes registrational CAR T-cell agents for numerous diseases, and a growing early-stage pipeline that expands cell and gene therapy targets, and technologies. We are developing cancer treatments directed at key biological pathways using our protein homeostasis platform, a research capability that has been the basis of our approved therapies for multiple myeloma and several promising compounds in early- to mid-stage development. Our scientists are targeting different immune system pathways to address interactions between tumors, the microenvironment and the immune system to further expand upon the progress we have made and help more patients respond to treatment. Combining these approaches is key to delivering new options for the treatment of cancer and addressing the growing issue of resistance to immunotherapy. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines a reality for patients.

About Lisocabtagene Maraleucel (liso-cel)

Liso-cel is an investigational chimeric antigen receptor (CAR) T-cell therapy designed to target CD19, which is a surface glycoprotein expressed during normal B-cell development and maintained following malignant transformation of B cells. Liso-cel aims to target CD19-expressing cells through a CAR construct that includes an anti-CD19 single-chain variable fragment (scFv) targeting domain for antigen specificity, a transmembrane domain, a 4-1BB costimulatory domain hypothesized to increase T-cell proliferation and persistence, and a CD3-zeta T-cell activation domain. The defined composition of CAR-positive viable T-cells (consisting of CD8 and CD4 components) in liso-cel may reduce product variability; however, the clinical significance of defined composition is unknown.

About TRANSCEND NHL 001

TRANSCEND NHL 001 is an open-label, multicenter, pivotal phase 1 study to determine the safety, antitumor activity, and pharmacokinetics of liso-cel in patients with R/R B-cell NHL, including DLBCL, HGL, PMBCL, Grade 3B FL. Mantle cell lymphoma is investigated in a separate cohort. The primary outcome measures included treatment-related adverse events, dose-limiting toxicities and objective response rate. Key secondary outcome measures included complete response rate, duration of response, and progression-free survival. The TRANSCEND program is a broad clinical program evaluating liso-cel in multiple disease states and treatment stages.

On February 13, 2020 Bio-Rad Laboratories, Inc. (NYSE: BIO and BIOb), a global leader of life science research and clinical diagnostic products, reported financial results for the fourth quarter and full year ended December 31, 2019 (Press release, Bio-Rad Laboratories, FEB 13, 2020, View Source [SID1234554315]).

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Fourth-quarter 2019 net sales were $624.4 million, an increase of 1.2 percent compared to $616.8 million reported for the fourth quarter of 2018. On a currency-neutral basis, quarterly sales increased 2.3 percent compared to the same period in 2018. Fourth-quarter gross margin was 52.9 percent compared to 53.9 percent during the fourth quarter in 2018. As previously disclosed, we experienced a cyberattack on our network on December 5, 2019. We immediately took affected systems offline as part of our comprehensive response to contain the activity. We have since resumed normal operations, although this occurrence did have an impact on sales and operations during December 2019.

Life Science segment net sales for the fourth quarter were $242.0 million, an increase of 1.0 percent compared to the same period in 2018. On a currency-neutral basis, Life Science segment sales increased by 1.8 percent compared to the same quarter in 2018. Currency-neutral sales growth was primarily driven by growth of Process Media, Droplet Digital PCR and Food Safety products. On a geographic view, the sales increase was due to growth in North America and Europe.

Clinical Diagnostics segment net sales for the fourth quarter were $379.0 million, an increase of 1.6 percent compared to the same period in 2018. On a currency-neutral basis, net sales were up 2.8 percent compared to the same quarter last year. Currency-neutral sales were primarily attributed to Diabetes, Quality Controls, Autoimmune, and Blood Typing products. Sales increase during the fourth quarter of 2019 was the result of growth in Asia and the Americas.

Net income for the fourth quarter of 2019 was $553.5 million, or $18.31 per share on a diluted basis, compared to a net loss of ($828.5) million, or ($27.73) per share on a diluted basis, during the same period in 2018. Net income for the fourth quarter of 2019 was significantly and favorably impacted by the recognition on the income statement of changes in the fair market value of equity securities reflecting an increase in value of $646.0 million during the fourth quarter of 2019, primarily related to our holdings of Sartorius AG.

The effective tax rate for the fourth quarter of 2019 was 20.9 percent, compared to 20.4 percent for the same period in 2018.

"Aside from the impact of the cyberattack on our network in December, sales performance for the fourth quarter reflected continued momentum of many of our key life science and diagnostic product lines," said Norman Schwartz, Bio-Rad President and Chief Executive Officer. "Looking back at the year, we are encouraged by our overall performance, in particular, our core operating results that provide us with good momentum toward continued topline growth and reaching our long-term goals as we head into 2020."

A reconciliation between GAAP operating results and non-GAAP operating results is provided following the financial statements that are part of this press release. Non-GAAP adjustments include amortization of purchased intangibles; acquisition-related expenses and benefits; restructuring, impairment charges and valuation changes in equity-owned investments; gains and losses on equity-method investments; significant litigation charges or benefits and legal costs; and, discrete income tax events and the income tax effect on these non-GAAP adjustments.

Non-GAAP net income and non-GAAP diluted income per share (non-GAAP EPS) are non-GAAP measures that exclude certain items detailed later in this press release under the heading "Non-GAAP Reporting."

Non-GAAP net income for the fourth quarter of 2019 was $70.0 million, or $2.32 per share on a diluted basis, compared to $63.1 million, or $2.09 per share on a diluted basis, during the same period in 2018. The non-GAAP effective tax rate for the fourth quarter of 2019 was 17.7 percent, compared to 28.7 percent for the same period in 2018. The lower rate in 2019 was largely driven by favorable regulatory guidance relating to U.S. Tax reform issued in the fourth quarter of 2019.

The following table represents a reconciliation of Bio-Rad’s reported net income and diluted income per share to non-GAAP net income and non-GAAP diluted income per share for the three months and for the full year ended December 31, 2019 and 2018:

Full Year 2019 Results

On a reported basis, net sales for the full year of 2019 increased 1.0 percent to $2,311.7 million compared to $2,289.4 million for the full year of 2018. On a currency-neutral basis, net sales grew 3.3 percent. Full-year reported net sales for the Life Science segment were $885.9 million, an increase of 2.8 percent compared to 2018. On a currency-neutral basis sales increased 4.6 percent versus 2018. Full-year reported net sales for the Clinical Diagnostics segment were $1,412.0 million, flat compared to 2018, or an increase of 2.8 percent on a currency-neutral basis. Full-year gross margin was 54.4 percent, compared to 53.4 percent during the same period in 2018.

Net income for 2019 was $1,758.7 million, or $58.27 per share on a fully diluted basis, compared to $365.6 million, or $12.10 per share, respectively, during the same period in 2018. This significant increase was primarily due to the change in fair market value of our equity securities in 2019 primarily related to our holdings of Sartorius AG.

The effective tax rate in 2019 was 22.2 percent compared to 28.7 percent in 2018. The tax rate in 2019 and 2018 was driven by the large unrealized gain in equity securities. The rate in 2018 was also impacted by our accounting for U.S. Tax reform and non-deductible goodwill impairment.

2019 Full-Year Highlights

Full-year sales were $2,311.7 million compared to $2,289.4 million for the full year of 2018. After normalizing for the impact of currency, full-year sales increased 3.3 percent.
Year-to-date net income for 2019 was $1,758.7 million, or $58.27 per share on a fully diluted basis, compared to $365.6 million, or $12.10 per share, respectively, during the same period in 2018.
In February, Bio-Rad’s QXDx AutoDG ddPCR System and QXDx BCR-ABL %IS Kit were the industry’s first digital PCR products to receive U.S. Food and Drug Administration (FDA) clearance. The system uses Bio-Rad’s Droplet Digital PCR (ddPCR) technology to monitor and quantitate the molecular response of chronic myeloid leukemia patients undergoing tyrosine kinase inhibitor therapy.
During the second quarter, Bio-Rad announced the launch of an innovative test to aid in the diagnosis of Lyme disease with the FDA clearance of its BioPlex 2200 Lyme Total Assay. Also during the second quarter, Bio-Rad’s IH-500 automated random access system for blood typing and screening, received FDA 510(k) clearance.
In April, Bio-Rad named Ilan Daskal as Executive Vice President and Chief Financial Officer and Andrew Last as Executive Vice President and Chief Operating Officer.
In June, Bio-Rad announced the launch of its scATAC-Seq solution, a single-cell assay for transposase-accessible chromatin using sequencing, offering high capture efficiency and sensitivity for profiling of gene regulation of individual human cells.
In August, Bio-Rad acquired Exact Diagnostics, a leading provider of a broad range of molecular diagnostics controls. With this acquisition, Bio-Rad expanded its line of quality control products in the area of transplant, respiratory, virology, microbiology, sexually transmitted infections, and vector-borne diseases.
In November, Bio-Rad installed its QX ONE Droplet Digital PCR System at select customer labs prior to the official product launch. The system automates the company’s Droplet Digital technology into a single integrated instrument designed for drug development and manufacturing quality control as well as other highly critical testing environments.
2020 Financial Outlook

For the full year 2020, the company anticipates currency-neutral revenue growth of approximately 4.5 to 5.25 percent and improved profitability with an estimated non-GAAP operating margin of 13.8 to 14.3 percent. Management will discuss this outlook in greater detail on the fourth-quarter and full-year 2019 financial results conference call.

"Looking ahead to 2020, we expect another year of progress driven by a combination of healthy markets, new products, and a focus on operating efficiencies," Mr. Schwartz said. "We continue to pursue our goal of 20 percent adjusted EBITDA run rate by the end of the year."

Non-GAAP Reporting

In addition to the financial measures prepared in accordance with generally accepted accounting principles (GAAP), we use certain non-GAAP financial measures, including non-GAAP net income and non-GAAP EPS, which exclude amortization of acquisition-related intangible assets, certain acquisition-related expenses and benefits, restructuring charges, asset impairment charges, valuation changes of equity owned investments, gains and losses on equity-method investments, and significant legal-related charges or benefits and associated legal costs. Non-GAAP net income and non-GAAP EPS also exclude certain other gains and losses that are either isolated or cannot be expected to occur again with any predictability, tax provisions/benefits related to the previous items, and significant discrete tax events. We exclude the above items because they are outside of our normal operations and/or, in certain cases, are difficult to forecast accurately for future periods.

We utilize a number of different financial measures, both GAAP and non-GAAP, in analyzing and assessing the overall performance of our business, in making operating decisions, forecasting and planning for future periods, and determining payments under compensation programs. We consider the use of the non-GAAP measures to be helpful in assessing the performance of the ongoing operation of our business. We believe that disclosing non-GAAP financial measures provides useful supplemental data that, while not a substitute for financial measures prepared in accordance with GAAP, allows for greater transparency in the review of our financial and operational performance. We also believe that disclosing non-GAAP financial measures provides useful information to investors and others in understanding and evaluating our operating results and future prospects in the same manner as management and in comparing financial results across accounting periods and to those of peer companies. More specifically, management adjusts for the excluded items for the following reasons:

Amortization of purchased intangible assets: we do not acquire businesses and assets on a predictable cycle. The amount of purchase price allocated to purchased intangible assets and the term of amortization can vary significantly and are unique to each acquisition or purchase. We believe that excluding amortization of purchased intangible assets allows the users of our financial statements to better review and understand the historic and current results of our operations, and also facilitates comparisons to peer companies.

Acquisition-related expenses and benefits: we incur expenses or benefits with respect to certain items associated with our acquisitions such as transaction costs; professional fees for assistance with the transaction; valuation or integration costs; changes in the fair value of contingent consideration; gain or loss on settlement of pre-existing relationships with the acquired entity; or adjustments to purchase price. We exclude such expenses or benefits as they are related to acquisitions and have no direct correlation to the operation of our on-going business.

Restructuring, impairment charges, valuation changes in equity owned investments and gains and losses on equity-method investments: we incur restructuring and impairment charges on individual or groups of employed assets, charges and benefits arising from valuation changes in equity owned investments and gains and losses on equity-method investments, which arise from unforeseen circumstances and/or often occur outside of the ordinary course of our on-going business. Although these events are reflected in our GAAP financials, these unique transactions may limit the comparability of our on-going operations with prior and future periods.

Significant litigation charges or benefits and legal costs: we may incur charges or benefits as well as legal costs in connection with litigation and other contingencies unrelated to our core operations. We exclude these charges or benefits, when significant, as well as legal costs associated with significant legal matters, because we do not believe they are reflective of on-going business and operating results.

Income tax expense: we estimate the tax effect of the excluded items identified above to determine a non-GAAP annual effective tax rate applied to the pretax amount in order to calculate the non-GAAP provision for income taxes. We also adjust for items for which the nature and/or tax jurisdiction requires the application of a specific tax rate or treatment.

From time to time in the future, there may be other items excluded if we believe that doing so is consistent with the goal of providing useful information to investors and management.

There are limitations in using non-GAAP financial measures because the non-GAAP financial measures are not prepared in accordance with generally accepted accounting principles and may be different from non-GAAP financial measures used by other companies. The non-GAAP financial measures are limited in value because they exclude certain items that may have a material impact on our reported financial results. The presentation of this additional information is not meant to be considered in isolation or as a substitute for the directly comparable financial measures prepared in accordance with GAAP in the United States. Investors should review the reconciliation of the non-GAAP financial measures to their most directly comparable GAAP financial measures as provided in the tables accompanying this press release.

Conference Call and Webcast

Management will discuss fourth quarter and full year ended December 31, 2019 results in a conference call at 2 PM Pacific Time (5 PM Eastern Time) February 13, 2020. Interested parties may access the call at 855-779-9068 within the U.S. or 631-485-4862 outside the U.S., Conference ID: 1397614. You may also listen to the conference call via a webcast that is available in the "Investor Relations" section of our website under "Quarterly Results" at www.bio-rad.com. The webcast will be available for up to a year.

On February 13, 2020 Medical Marijuana, Inc. (OTC: MJNA) (the "Company"), the first-ever publicly traded cannabis company in the United States that launched the world’s first-ever cannabis-derived nutraceutical products, brands and supply chain, reported that its portfolio investment company Kannalife, Inc. ("Kannalife") (OTC: KLFE), a biopharmaceutical company specializing in the research and development of cannabinoid therapeutics, has completed its phase 1 study funded by a grant (1R41DA044898-01) from the National Institutes of Health’s (NIH) National Institute on Drug Abuse (NIDA) (Press release, Medical Marijuana Sciences, FEB 13, 2020, https://www.prnewswire.com/news-releases/medical-marijuana-inc-portfolio-investment-company-kannalife-inc-announces-completion-of-nih-nida-phase-1-grant-and-results-from-temple-university-301004359.html [SID1234554333]).

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The study was performed by Kannalife and the Lewis Katz School of Medicine at Temple University (LKSOM) to assess KLS-13019, Kannalife’s patented cannabidiol (CBD)-like molecule, as a potential treatment of neuropathic pain and drug dependence.

"KLS-13019 continues to show potential as a much-needed treatment for CIPN," said Dr. Stuart Titus, CEO of Medical Marijuana, Inc. "According to a recent study conducted by RRI, it is estimated that the total global neuropathic pain market will be worth more than $8.3 billion by 2024."

The pre-clinical grant study was performed in an animal model to evaluate the potential use of KLS-13019 as a potent, non-opioid alternative in the prevention and reversal of chemotherapy-induced peripheral neuropathy (CIPN). The animal model portion of the study was conducted by Sara Jane Ward, Ph.D., Assistant Professor of Pharmacology at LKSOM.

"These recent study results suggest that Kannalife’s proprietary CBD-like molecule is at least as effective as CBD in preventing neuropathic pain in animal models. Even further, KLS-13019 goes a step further than CBD by showing the potential to reverse neuropathic pain," said Dean Petkanas, CEO of Kannalife. "Kannalife looks to bring effective new treatment options to market as soon as possible and this research puts us one step closer to that goal."

The completed study could lead to a Phase 2 grant and further advances Kannalife’s belief that KLS-13019 could become a viable drug candidate, and an alternative to opioids, as a treatment for patients suffering from CIPN and chronic pain management.

The research reported in this press release was supported by the National Institute on Drug Abuse (NIDA) of the National Institutes of Health (NIH) in the amount of $299,916 under award number 1R41DA044898-01.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

About KLS-13019
KLS-13019 is Kannalife’s leading proprietary investigational CBD-like product for the potential treatment of a range of neurodegenerative and neuropathic pain disorders, beginning with chemotherapy-induced peripheral neuropathy (CIPN). KLS-13019 has not been reviewed or approved for patient use by the U.S. Food and Drug Administration (FDA) or any other healthcare authority in the world. Its safety and efficacy have not been confirmed by FDA-approved research.

On February 13, 2020 Agios Pharmaceuticals, Inc. (NASDAQ: AGIO) reported business highlights and financial results for the fourth quarter and year ended December 31, 2019 (Press release, Agios Pharmaceuticals, FEB 13, 2020, View Source [SID1234554260]. In addition, Agios highlighted key 2020 corporate milestones and data presentations for its clinical development programs.

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"On the heels of a busy and productive 2019, I’m more confident than ever in the strength of our team and our ability to make a meaningful impact on the lives of patients through great science, a deep pipeline and differentiated therapies," said Jackie Fouse, Ph.D., chief executive officer at Agios. "In 2020, our clinical development team is focused on advancing our Phase 3 PK deficiency studies in order to submit a new drug application in 2021, finalizing our pivotal development plan for the PK activation program in thalassemia and establishing proof-of-concept in sickle cell disease. In addition, we are driving enrollment in several Phase 3 studies for our IDH inhibitors in both malignant hematology and solid tumors. Our commercial team is focused on achieving an ambitious revenue target for TIBSOVO and increasing market development activities in preparation for a potential launch in PK deficiency."

ANTICIPATED 2020 KEY MILESTONES

Agios expects the following key milestones in 2020:

Hematologic Malignancies

Deliver full-year U.S. revenue for TIBSOVO of $105-115 million
Receive European Medicines Agency CHMP opinion for TIBSOVO in relapsed or refractory acute myeloid leukemia (AML) with an IDH1 mutation by year-end
Complete enrollment of the Phase 3 AGILE trial of TIBSOVO in combination with azacitidine in adult patients with previously untreated IDH1 mutant AML by year-end
Complete enrollment of the relapsed or refractory myelodysplastic syndrome arm of the TIBSOVO Phase 1 study of IDH1 mutant advanced hematologic malignancies by year-end
Solid Tumors

File supplemental new drug application (sNDA) for TIBSOVO in previously treated IDH1 mutant cholangiocarcinoma by year-end
Rare Genetic Diseases

Announce topline data for ACTIVATE and ACTIVATE-T pivotal trials for mitapivat in adults with pyruvate kinase (PK) deficiency by year-end
Submit updated data from the Phase 2 study of mitapivat in thalassemia for presentation at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress in June and finalize pivotal development strategy by year-end
Achieve proof-of-concept for mitapivat in sickle cell disease by mid-2020
Receive investigational new drug (IND) clearance for AG-946, a next generation PKR activator, and initiate a first-in-human study in healthy volunteers in the first half of 2020
Research

Achieve at least one new development candidate by year-end
FOURTH QUARTER AND FULL YEAR 2019 FINANCIAL RESULTS

Revenue: Total revenue for the fourth quarter of 2019 was $35.4 million, which includes $12.9 million in collaboration revenue, $19.6 million of net product revenue from sales of TIBSOVO and $3.0 million in royalty revenue from net global sales of IDHIFA under our collaboration agreement with Celgene. This compares to $30.0 million for the fourth quarter of 2018, which included $18.4 million in collaboration revenue, $9.4 million of net product revenue from U.S. sales of TIBSOVO and $2.2 million in royalty revenue from net global sales of IDHIFA. Total revenue for the year ended December 31, 2019 was $117.9 million compared to $94.4 million for the year ended December 31, 2018. The increase in 2019 revenue was primarily driven by net U.S. sales of TIBSOVO and were offset by a decline in collaboration revenue due to the recognition of a milestone from Celgene and the upfront payment from CStone in 2018.

Cost of Sales: Cost of sales were $0.3 million for the fourth quarter of 2019 compared to $0.7 million for the fourth quarter of 2018, and $1.3 million for the year ended December 31, 2019 compared to $1.4 million for the comparable period in 2018.

Research and Development (R&D) Expenses: R&D expenses were $106.2 million for the fourth quarter of 2019 compared to $93.8 million for the fourth quarter of 2018 and $410.9 million for the year ended December 31, 2019 compared to $341.3 million for the comparable period in 2018. The increase in R&D expense was primarily attributable to clinical trial activity for mitapivat in PK deficiency and thalassemia; start-up costs for the vorasidenib Phase 3 INDIGO study in low-grade glioma, including required clinical pharmacology studies and companion diagnostic development; and ongoing enrollment in the TIBSOVO Phase 3 AGILE and HOVON frontline AML combination studies. R&D expense also increased as a result of ongoing research efforts across our discovery platform programs.

Selling, General and Administrative (SG&A) Expenses: SG&A expenses were $34.8 million for the fourth quarter of 2019 compared to $31.9 million for the fourth quarter of 2018, and $132.0 million for the year ended December 31, 2019 compared to $114.1 million for the year ended December 31, 2018. The increase in SG&A expense was primarily attributable to increased investment in marketing activities in preparation for the potential launch of mitapivat and personnel costs related to increased headcount to support growing operations.

Net Loss: Net loss was $102.4 million for the fourth quarter of 2019 compared to $91.8 million for the fourth quarter of 2018, and $411.5 million for the year ended December 31, 2019 compared to a net loss of $346.0 million for the year ended December 31, 2018.

Cash Position and Guidance: Cash, cash equivalents and marketable securities as of December 31, 2019 were $717.8 million compared to $805.4 million as of December 31, 2018. The change in cash was primarily driven by expenditures to fund operations of $464.4 million offset by the net proceeds of $277.2 million from the November follow-on offering and cash inflows of $99.3 million from product sales, stock option exercises, royalty revenue, and collaboration reimbursements and milestones. The company expects that its cash, cash equivalents and marketable securities as of December 31, 2019, together with anticipated product and royalty revenue, anticipated interest income, and anticipated expense reimbursements under our collaboration and license agreements, but excluding any additional collaboration-related payments, will enable the company to fund its anticipated operating expenses and capital expenditure requirements through at least the end of 2021.

CONFERENCE CALL INFORMATION

Agios will host a conference call and live webcast with slides today at 8:00 a.m. ET to discuss fourth quarter and full year 2019 financial results and recent business activities. To participate in the conference call, please dial 1-877-377-7098 (domestic) or 1-631-291-4547 (international) and referring to conference ID 4195413. The live webcast can be accessed under "Events & Presentations" in the Investors section of the company’s website at www.agios.com. The archived webcast will be available on the company’s website beginning approximately two hours after the event.

About Agios/Celgene Collaboration
IDHIFA (enasidenib) and AG-270 are part of our collaboration with Celgene Corporation, a wholly owned subsidiary of Bristol-Myers Squibb Company. Under the terms of our 2010 collaboration agreement focused on cancer metabolism, Celgene has worldwide development and commercialization rights for IDHIFA. Agios continues to conduct certain clinical development activities within the IDHIFA development program and is eligible to receive reimbursement for those development activities and up to $80 million in remaining milestone payments, and royalties on any net sales. Celgene and Agios are currently co-commercializing IDHIFA in the U.S. Celgene will reimburse Agios for costs incurred for its co-commercialization efforts. AG-270 is part of a 2016 global research collaboration agreement with Celgene focused on metabolic immuno-oncology. Celgene has the option to participate in a worldwide 50/50 cost and profit share with Agios, under which Agios is eligible for up to $169 million in clinical and regulatory milestone payments for the program.

On February 13, 2020 Bonnie J Addario Lung Cancer Foundation reported that Patients with lung cancer face the challenge of drug resistance, while researchers focus on extending treatment duration (Press release, Bonnie J Adodario Lung Cancer Fundation, FEB 13, 2020, View Source [SID1234554284]). In collaboration with the patient group ALK Positive, we have awarded a new research collaboration grant dedicated to overcoming ALK+ treatment resistance.

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ALK mutations occur in nearly 5% of patients with non-small cell lung cancer (NSCLC). Currently, five ALK-specific inhibitors (alectinib, brigatinib, ceritinib, crizotinib, and lorlatinib) have greatly extended the lives of patients. The downside is that drug resistance kicks in far too often. The search for innovative approaches to prevent drug resistance and extend treatment duration is imperative to ALK+ patients and to all individuals living with lung cancer.

This grant was awarded to Dr. Trever Bivona, associate professor of medicine at the University of California – San Francisco, and Dr. Christine Lovly, associate professor of medicine at Vanderbilt University Medical Center. The research will focus on understanding why ALK specific drugs stop working and will test the use of drug combinations to delay or prevent resistance. The project is entitled "Transforming ALK+ lung cancer into a chronic or curable condition by combating drug resistance."

This collaboration seeks to fill key knowledge gaps in our understanding of ALK inhibitor response and resistance, with an overarching goal of identifying new targets that improve responses to ALK inhibitor therapy and, ultimately, improve the quantity and quality of life for patients. The project was selected after a rigorous internal and external review process by a committee consisting of patients living with ALK+ NSCLC and some of the world’s foremost ALK experts.

In this era of precision medicine, patients are disrupting the research paradigm by funding and selecting projects that deliver maximum benefit to their community. All of us at GO2 Foundation are pleased to partner with ALK Positive on this research collaboration grant. We look forward to continuing to fuel life-saving research.

Please help save, extend, and improve the lives of those vulnerable, at risk, and living with lung cancer and make a contribution today.