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

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

2018 Highlights

Clinical

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

Regulatory

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

Research

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

Corporate

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

2019 Updates

Clinical

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

Regulatory

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

Research

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

Fourth Quarter 2018 Financial Results

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

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

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

Full Year 2018 Financial Results

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

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

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

Cash, Cash Equivalents and Short-term Investments

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

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

Webcast and Conference Call

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

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

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

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

On February 27, 2019 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported recent business highlights, anticipated upcoming milestones, and financial results for the fourth quarter and full year of 2018 (Press release, BeiGene, FEB 27, 2019, View Source/phoenix.zhtml?c=254246&" target="_blank" title="View Source/phoenix.zhtml?c=254246&" rel="nofollow">View Source;p=RssLanding&cat=news&id=2389335 [SID1234533788]).

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

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

Recent Business Highlights and Upcoming Milestones

Clinical Programs

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

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

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

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

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

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

Announce top-line results from the pivotal Phase 2 trial in Chinese patients with previously treated ovarian cancer in late 2019 or early 2020; and
Present data in patients with ovarian cancer from the global Phase 1 trial and updated Phase 1 combination data.
Sitravatinib, an investigational tyrosine kinase inhibitor of receptor tyrosine kinases (RTKs), including TAM family receptors (TYRO3, Axl, MER), split family receptors (VEGFR2, KIT) and RET, licensed from Mirati Therapeutics in Asia (excluding Japan), Australia, and New Zealand

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

On February 27, 2019 Perrigo Company plc (NYSE; TASE: PRGO) reported financial results for the fourth quarter and calendar year ended December 31, 2018 (Press release, Perrigo Company, FEB 27, 2019, View Source [SID1234533845]).

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Perrigo President and CEO Murray S. Kessler commented, "While 2018 was a difficult year for Perrigo, significant progress was made in the fourth quarter against the Company’s transformation plans. Market share in our consumer businesses were stable for the year, and the Company met its updated full-year 2018 guidance expectations despite an unusual equipment start-up issue at one of our facilities that resulted in a fourth quarter adjusted EPS headwind of approximately $0.08. It was also encouraging to see a meaningful, sequential improvement in the RX segment during the fourth quarter, as downward pricing pressure eased."

Kessler continued, "While the Company is facing a number of challenges, I am pleased with the rapid progress our team is making on its transformation plans and evolution from a healthcare company to a consumer self-care company. We are continuing to make significant progress with the separation of the RX business and recently received the $250 million milestone payment related to Tysabri."

Kessler concluded, "We look forward to sharing our strategy as well as providing demonstrable progress at our Investor Day presentation on May 9, 2019 in New York City. Investors can expect to see the Company’s plans for portfolio reconfiguration, capacity and technology investments, innovation initiatives, cost savings plans to help fuel growth, capital allocation plans, organizational effectiveness initiatives and calendar 2019 guidance at that time. While there is much work to do, I remain excited and confident in our ability to recapture the ‘Perrigo Advantage’ and bring the Company back to profitable and sustainable growth."

Refer to Tables I – VI at the end of this press release for a reconciliation of non-GAAP measures to the current year and prior year periods and additional non-GAAP information. The Company’s reported results are included in the attached Condensed Consolidated Statements of Operations, Balance Sheets and Statements of Cash Flows.

Calendar year 2017 net sales have been adjusted to exclude approximately $21 million of sales attributable to the divested Israel API business.

Reported net sales for calendar year 2018 were approximately $4.7 billion, which included new product sales of $170 million, partially offset by discontinued products of $66 million. Adjusted net sales decreased 4.6% on a constant currency basis. Unfavorable currency movements impacted net sales by $34 million.

Reported net income was $131 million, or $0.95 per diluted share, versus $120 million, or $0.84 per diluted share, in the prior year. Excluding charges as outlined in Table I, calendar year 2018 adjusted net income was $629 million, or $4.55 per diluted share, versus $703 million, or $4.93 per diluted share, last year.

Fourth Quarter Results

Fourth quarter 2017 net sales have been adjusted to exclude approximately $4 million of sales attributable to the divested Israel API business.

Net sales for the fourth quarter of calendar year 2018 were approximately $1.2 billion, which included new product sales of $51 million, partially offset by discontinued products of $16 million. Adjusted net sales decreased 5.1% on a constant currency basis. Unfavorable currency movements impacted net sales by $18 million.

Reported net income was $82 million, or $0.60 per diluted share, versus $73 million, or $0.52 per diluted share, in the prior year. Excluding charges as outlined in Table I, fourth quarter 2018 adjusted net income was $132 million, or $0.97 per diluted share, versus $180 million, or $1.28 per diluted share, for the same period last year.

CHC Americas segment net sales were down 4.1% compared to last year. Net sales in the analgesics and smoking cessation categories coupled with new product sales of $10 million, were more than offset by lower net sales in the animal health and nutrition categories. Discontinued products in the quarter were $10 million, of which $6 million related to the animal health business. Excluding the animal health business, CHC Americas net sales decreased approximately 1.9% on a constant currency basis.

CHC Americas’ fourth quarter reported gross profit margin was 29.5%. Adjusted gross profit margin was 30.4% or 560 bps lower than the prior year. The majority of this decline was due to an unusual equipment startup issue at one facility, higher input costs and greater operating inefficiencies, including service-related challenges.

Reported fourth quarter operating margin was 16.4%. Fourth quarter adjusted operating margin was 18.0%, lower than the prior year due primarily to adjusted gross margin flow through, partially offset by lower administrative expenses.

CHC International net sales were relatively flat, excluding $2 million in net sales from exited businesses in 2017 and unfavorable foreign currency movements of $17 million. Net sales in the diagnostics and analgesics categories, in addition to new product sales of $19 million, were mostly offset by lower net sales in the lifestyle and cough cold categories. The absence of net sales from discontinued products was $2 million.

Reported and adjusted gross margin decreased 110 bps versus a year ago due primarily to less favorable product mix.

Reported operating margin was (0.5)%. Adjusted operating margin decreased 240 basis points to 12.9%. Growth investments in advertising and R&D increased approximately 350 bps as a percentage of net sales compared to prior year. These increases were partially offset by lower selling and administrative expenses.

RX net sales were $222 million in the quarter, lower than the prior year due primarily to industry dynamics, including pricing pressure, supply constraints in a few products and discontinued products of $4 million. New product sales were $22 million.

Reported gross margin was 45.5%. Adjusted gross margin was 54.8%, or 160 bps higher than the same quarter last year, driven primarily by new product launches.

Reported operating margin was 30.5%. Adjusted operating margin was 39.2%, or 110 bps higher than the prior year due primarily to adjusted gross margin flow through while maintaining R&D dollar investments for growth.

Conference Call

The Company will host a conference call at 4:30 p.m. EST (1:30 p.m. PST), February 27, 2019. The conference call will be available live via webcast to interested parties in the investor relations section of the Perrigo website at View Source or by phone at 888-317-6003, International 412-317-6061, and reference ID # 0121144. A taped replay of the call will be available beginning at approximately 8:00 p.m. (EST) Wednesday, February 27, 2019, until midnight March 6, 2019. To listen to the replay, dial 877-344-7529, International 412-317-0088, and use access code 10128203.

On February 27, 2019 PRA Health Sciences, Inc. ("PRA" or the "Company") (NASDAQ: PRAH) reported financial results for the quarter and year ended December 31, 2018 (Press release, PRA Health Sciences, FEB 27, 2019, View Source;p=irol-newsArticle&ID=2389364 [SID1234533741])

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"We are delighted to have closed out 2018 with another quarter of strong financial results," said Colin Shannon, PRA’s Chief Executive Officer. "Our ability to execute across all of our businesses has allowed us to deliver solid revenue growth and strong bottom-line results. Our key financial metrics continue to improve, as highlighted by our 1.30 net book-to-bill ratio and our expanding margins. We remain focused on providing broad and flexible services to our clients and believe we are well positioned to deliver strong results in 2019."

Net new business for our Clinical Research segment for the three months ended December 31, 2018 was $667.3 million, representing a net book-to-bill ratio of 1.30 for the period. This net new business contributed to an ending backlog of $4.2 billion at December 31, 2018.

For the three months ended December 31, 2018, revenue was $729.6 million, which represents growth of 11.2%, or $73.8 million, compared to the fourth quarter of 2017 at actual foreign exchange rates. On a constant currency basis, revenue grew $79.0 million, an increase of 12.0% compared to the fourth quarter of 2017. By segment, the Clinical Research segment generated revenues of $655.6 million, while the Data Solutions segment generated revenues of $74.0 million.

On January 1, 2018, the Company adopted Accounting Standards Codification Topic 606, "Revenue from Contracts with Customers," or ASC 606, using the modified retrospective method for all contracts that were not completed as of January 1, 2018. Prior periods have not been restated under this guidance and remain as previously reported. The primary impact of applying this new guidance on our statement of operations is that (i) we now recognize reimbursements from our customers for payments to investigators as revenue, whereas these payments and costs were previously recorded on a net basis, and (ii) we include all reimbursed costs in the total project costs when measuring our progress under our research contracts instead of recording these amounts on a separate basis.

Excluding the impact of the adoption of ASC 606 and reimbursement revenue, revenue increased $20.2 million, which represents growth of 3.6% at actual foreign exchange rates and 4.2% on a constant currency basis.

Direct costs, exclusive of depreciation and amortization, were $365.7 million during the three months ended December 31, 2018 compared to $368.9 million for the three months ended December 31, 2017. The decrease in direct costs was primarily due to a favorable impact of $8.6 million from foreign currency exchange rate fluctuations, which was offset by an increase in salaries and related benefits of $3.6 million in our Clinical Research segment as we continue to ensure appropriate staffing levels and an increase of $1.6 million in our Data Solutions segment. Direct costs were 50.1% of revenue during the fourth quarter of 2018 compared to 56.2% of revenue during the fourth quarter of 2017. Excluding the impact of the adoption of ASC 606 and reimbursement revenue, direct costs were 62.1% of revenue during the fourth quarter of 2018 compared to 64.9% of revenue during the fourth quarter of 2017.

Selling, general and administrative expenses were $96.4 million during the three months ended December 31, 2018 compared to $92.2 million for the three months ended December 31, 2017. Excluding the impact of the adoption of ASC 606 and reimbursement revenue, selling, general and administrative costs were 16.4% of revenue during the fourth quarter of 2018 compared to 16.2% of revenue during the fourth quarter of 2017.

GAAP net income was $71.5 million for the three months ended December 31, 2018, or $1.07 per share on a diluted basis, compared to a GAAP net loss of $16.0 million for the three months ended December 31, 2017, or $0.25 per share on a diluted basis. Our reported net loss for the three months ended December 31, 2017 included the loss on modification of debt and the revaluation of acquisition-related earn-out liabilities.

EBITDA was $124.9 million for the three months ended December 31, 2018, representing an increase of 720.9% compared to the three months ended December 31, 2017. Our EBITDA for the three months ended December 31, 2017 included the loss on modification of debt and the revaluation of acquisition-related earn-out liabilities. Adjusted EBITDA was $136.2 million for the three months ended December 31, 2018, representing growth of 18.8% compared to the three months ended December 31, 2017.

Adjusted net income was $86.9 million for the three months ended December 31, 2018, representing 26.4% growth compared to the three months ended December 31, 2017. Adjusted net income per diluted share was $1.31 for the three months ended December 31, 2018, representing 26.0% growth compared to the three months ended December 31, 2017.

Full Year 2018 Financial Highlights

For the twelve months ended December 31, 2018, revenue was $2,871.9 million, which represents growth of 27.1%, or $612.5 million, compared to the twelve months ended December 31, 2017 at actual foreign exchange rates. On a constant currency basis, revenue grew $597.3 million, representing growth of 26.4% compared to the twelve months ended December 31, 2017. By segment, the Clinical Research segment generated revenues of $2,622.4 million, while the Data Solutions segment generated revenues of $249.5 million.

Excluding the impact of the adoption of ASC 606 and reimbursement revenue, revenue increased $348.5 million, which represents growth of 17.9% at actual foreign exchange rates and 17.4% on a constant currency basis. Organic revenue growth, excluding the adoption of ASC 606, reimbursement revenue and revenue attributable to our Data Solutions segment, was 10.2% at actual foreign exchange rates and 9.7% on a constant currency basis.

Reported GAAP income from operations was $281.3 million, reported GAAP net income attributable to PRA Health Sciences was $153.9 million and reported GAAP net income attributable to PRA Health Sciences per diluted share was $2.32 for the twelve months ended December 31, 2018.

Adjusted net income was $284.1 million for the twelve months ended December 31, 2018, an improvement of 29.8% compared to the twelve months ended December 31, 2017. Adjusted net income per diluted share was $4.28 for the twelve months ended December 31, 2018, up 28.5% compared to the twelve months ended December 31, 2017.

Full Year 2019 and Q1 2019 Guidance

For full year 2019, the Company expects to achieve total revenues between $3.09 billion and $3.20 billion, representing as reported and constant currency growth of 8% to 11%. On an ASC 605 basis, the Company expects to achieve revenues of between $2.475 billion and $2.57 billion, representing as reported and constant currency growth of 8% to 12%.

We expect GAAP net income per diluted share of between $3.65 and $3.80 per share and adjusted net income per diluted share of between $4.93 and $5.08 per share, representing growth of 15% to 19%. We anticipate an annual effective income tax rate estimate of 24%.

Our effective tax rate may differ from this estimate, due to, among other things, changes to estimates of the geographic allocation of our pre-tax income as well as changes in interpretations, analysis, and additional guidance that may be issued by regulatory agencies as it relates to the Tax Cuts and Jobs Act.

For Q1 2019, the Company expects to achieve total revenues between $720.0 million and $740.0 million, representing as reported growth of 3% to 5% and constant currency growth of 4% to 7%. On an ASC 605 basis, the Company expects to achieve revenues of between $575.0 million and $595.0 million, representing as reported growth of 3% to 6% and constant currency growth of 4% to 7%. The Company expects GAAP net income per diluted share of between $0.74 and $0.79 per share, adjusted net income per diluted share between $1.05 and $1.10 per share, and an annual effective income tax rate of 24%.

Our 2019 guidance assumes a EURO rate of 1.15 and a GBP rate of 1.35 with all other foreign currencies using a rate as of January 31, 2019.

A reconciliation of our non-GAAP measures, including revenue reported on an ASC 605 basis, EBITDA, adjusted EBITDA, adjusted net income, adjusted net income per share and our 2019 guidance, to the corresponding GAAP measures is included in this press release.

Conference Call Details

PRA will host a conference call at 9:00 a.m. ET on February 28, 2019, to discuss the contents of this release and other relevant topics. To participate, please dial (877) 930-8062 within the United States or (253) 336-7647 outside the United States approximately 10 minutes before the scheduled start of the call. The conference ID for the call is 8697447. The conference call will also be accessible, live via audio broadcast, on the Investor Relations section of the PRA website at investors.prahs.com. A replay of the conference call will be available online at investors.prahs.com. In addition, an audio replay of the call will be available for one week following the call and can be accessed by dialing (855) 859-2056 within the United States or (404) 537-3406 outside the United States. The replay ID is 8697447.

Additional Information

A financial supplement with fourth quarter 2018 results, which should be read in conjunction with this press release, may be found in the Investor Relations section of our website at investors.prahs.com in a document titled "Q4 2018 Earnings Presentation."

On February 27, 2019 Syndax Pharmaceuticals, Inc. ("Syndax," the "Company" or "we") (Nasdaq:SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported two oral presentations at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held March 29 – April 3, 2019 in Atlanta, Georgia (Press release, Syndax, FEB 27, 2019, View Source [SID1234533761]).

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Oral Presentation Details

Title: Identification of gene signatures associated with response in a Phase 2 trial of entinostat (ENT) plus pembrolizumab (PEMBRO) in non-small cell lung cancer (NSCLC) patients whose disease has progressed on or after anti-PD-(L)1 therapy
First author: Peter Ordentlich, Ph.D.
Session: Advances in Novel Immunotherapeutics (Clinical Trials Minisymposium)
Abstract Number: 7822
Location: Georgia World Congress Center, Building A, Room 411
Date and Time: Sunday, March 31, 2019; 3:00 p.m. – 5:00 p.m. ET

Title: Efficacy and safety of entinostat (ENT) and pembrolizumab (PEMBRO) in patients with melanoma previously treated with anti-PD1 therapy
First author: Ryan Sullivan, M.D.
Session: Optimizing PD-1/PD-L1 Immune Checkpoint Inhibitor Therapy (Clinical Trials Plenary Session)
Abstract Number: 7449
Location: Georgia World Congress Center, Building A, Marcus Auditorium
Date and Time: Monday, April 1, 2019; 10:30 a.m. – 12:30 p.m. ET

All accepted abstracts will be published in the 2019 Proceedings of the AACR (Free AACR Whitepaper). Session information is available online via the Annual Meeting Itinerary Planner through the AACR (Free AACR Whitepaper) website at www.aacr.org.