Onxeo to Present Five Preclinical Studies Highlighting AsiDNA™ Unique Profile and its clinical potential in Oncology at 2019 American Association for Cancer Research Annual Meeting

On February 13, 2019 Onxeo S.A. (Euronext Paris, NASDAQ Copenhagen: ONXEO), ("Onxeo" or "the Company"), a clinical-stage biotechnology company specializing in the development of innovative drugs targeting tumor DNA Damage response (DDR) in oncology, in particular against rare or resistant cancers, reported that results of five preclinical study supporting the differentiated profile of AsiDNA, its first-in-class DNA Damage Response (DDR) inhibitor, including insights into the compound’s unique mechanism of action, will be presented at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held March 29 – April 3, 2019, in Atlanta, GA, USA (Press release, Onxeo, FEB 13, 2019, View Source [SID1234533278]).

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Françoise Bono, PhD, Chief Scientific Officer, commented: "We are thrilled to have had five AsiDNA-related abstracts accepted for presentation at this prestigious meeting of oncology, including 2 abstracts resulting from our long-standing collaboration with Institut Curie, an internationally recognized research institution. The study to be presented notably support the absence of the emergence of resistance to AsiDNA after repeated treatments and the abrogation of acquired resistance to PARP inhibitors when administered in combination with AsiDNA, two properties that make AsiDNA so distinctive and sustain its promising potential for future utilization in clinic. New data also provide valuable insights into the underlying mechanisms supporting these unique outcomes and their potential benefits in oncology. Furthermore, we have identified predictive biomarkers of sensitivity to AsiDNA, a strong advantage to optimize its clinical development and which could, ultimately, open the way to personalized medicine with AsiDNA. Lastly, these results expand the solid preclinical package on AsiDNA, further support the strong rationale for its ongoing development in the clinical setting and confirm its interest and its value in our company portfolio."

Titles of the five abstracts to be presented during poster sessions are:

AsiDNA, a targeted therapy with no acquired resistance
AsiDNA abrogates acquired resistance to PARP inhibitors
Molecular analysis of the mechanism of action of AsiDNA brings new clues on DNA damage response regulation
Development of a biomarker-driven patient selection strategy for AsiDNA treatment (in collaboration with Institut Curie)
AsiDNA, a novel DNA repair inhibitor to sensitize aggressive medulloblastoma subtypes (Institut Curie)
Details on the date, time and location of the sessions during the congress will be provided when available.

CAMBREX REPORTS FOURTH QUARTER AND FULL YEAR 2018

On February 13, 2019 Cambrex Corporation (NYSE: CBM), a leading provider of development, manufacturing, testing and technology services for small molecules, reported results for the fourth quarter and full year ended December 31, 2018 (Press release, Cambrex, FEB 13, 2019, View Source [SID1234533274]).

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Fourth Quarter 2018 Highlights

Announced the acquisition of Avista Pharma Solutions ("Avista"), an early clinical phase Contract Development, Manufacturing and Testing Organization, for approximately $252 million in total cash consideration. This transaction closed on January 2, 2019.

Net revenue was $134.3 million under current U.S. GAAP, ASC 606 ("ASC 606"). Under ASC 605, the previous revenue recognition standard, and the only standard under which fourth quarter 2017 results were reported, Net revenue increased 16% compared to the same quarter last year.

Under current U.S. GAAP, Income from continuing operations was $1.3 million and Diluted EPS was $0.04 per share. This reflects the impacts of the timing of certain tax charges related to tax reform in New Jersey. Under previous U.S. GAAP utilizing ASC 605, Income from continuing operations would have been $32.3 million and Diluted EPS from continuing operations would have been $0.96 per share compared to Income from continuing operations of $40.2 million and Diluted EPS of $1.20 in the same quarter last year. Adjusted Income from continuing operations was $48.7 million and Diluted EPS was $1.44, compared to $42.3 million and $1.26, respectively, for the same quarter last year (see table at the end of this press release).

Under ASC 606, EBITDA was $33.5 million. Adjusted EBITDA, which excludes the impact of adopting ASC 606, Halo’s results and Acquisition and Integration costs, was $70.7 million compared to $65.1 million in the same quarter last year (see table at the end of this press release).

Net debt was $204.1 million at the end of the quarter, a decrease of $23.7 million during the quarter primarily driven by cash flows from operations.

The Company expects full year 2019 Net revenue, which excludes the impact of foreign currency, to be between 21% and 25% higher than 2018 Net revenue as recorded under ASC 606 for both years. Adjusted EBITDA is expected to be between $150 and $160 million (see Financial Expectations – Continuing Operations section below for related explanations and additional financial guidance).

"We’re very excited to add the early stage development and testing capabilities of Avista Pharma, which when added to the drug product capabilities of Halo Pharma, which we acquired a few months ago, and Cambrex’s legacy drug substance capabilities, makes us a leading global provider of end to end integrated services for small molecules. Combining Cambrex, Halo and Avista will allow us to follow a small molecule from pre-clinical through commercialization and leverage hundreds of new customers and molecule opportunities across a much broader services and manufacturing platform. Integration efforts are well under way with the goal of building a best-in-class fully integrated contract development and manufacturing organization," commented Steven M. Klosk, President and Chief Executive Officer of Cambrex.

"Looking forward, we continue to see strong market conditions in the sectors that we serve. This is especially true in early stage development and testing, where we expect continued strong growth, creating the potential for a large funnel of molecules for which we hope to deliver a broad range of services all the way through commercial approval."

Basis of Reporting

The Company has provided a reconciliation of GAAP to adjusted (i.e. Non-GAAP) amounts at the end of this press release. Cambrex management believes that the adjustments provide useful information to investors due to the magnitude and nature of certain amounts recorded under GAAP.

Fourth Quarter 2018 Operating Results – Consolidated, Continuing Operations

Net revenue under ASC 606 was $134.3 million. Under ASC 605, the revenue recognition standard for which 2017 results were reported, Net revenue increased to $212.3 million, or 16%, from $182.3 million in the same quarter last year. Results under ASC 605 include a 2% unfavorable impact of foreign exchange compared to the fourth quarter of 2017. Net revenue during the fourth quarter of 2018 includes the acquisition of Halo, now our finished dosage form segment, which contributed revenue of $23.4 million under ASC 606 and $23.2 million under ASC 605. Excluding finished dosage form Net revenues, higher sales of controlled substances was the primary driver of the increase under ASC 605 compared to the same quarter last year.

Gross margin under ASC 606 was 36% for the fourth quarter of 2018. Under ASC 605, Gross margin was 41% compared to 43% in the same quarter last year. Excluding the finished dosage form segment and the unfavorable impact of foreign exchange, ASC 605 Gross margin during the quarter was 42%.

Selling, general and administrative expenses were $21.5 million, compared to $18.3 million in the same quarter last year. The increase was mainly due to higher amortization expense related to purchased intangible assets of $3.0 million within the finished dosage form segment.

Research and development expenses were $3.6 million, compared to $4.3 million in the same quarter last year. The decrease is primarily due to lower expenses related to the development of generic drug products.

Acquisition and Integration expenses of $3.4 million for the fourth quarter of 2018 represent costs associated with the acquisitions of Halo and Avista. The acquisition of Avista closed on January 2, 2019.

Operating profit under ASC 606 was $19.8 million for the fourth quarter of 2018. Under ASC 605, Operating profit was $58.8 million compared to $56.3 million in the same quarter last year. The increase was primarily the result of higher gross profit partially offset by higher operating expenses as described above. Adjusted EBITDA was $70.7 million compared to $65.1 million in the same quarter last year (see table at the end of this press release).

Income tax expense under ASC 606 was $17.5 million resulting in an effective tax rate of 93% compared to $15.6 million and an effective tax rate of 28% in the same quarter last year. Income tax expense during the quarter reflects $11.4 million of expense primarily for a state valuation allowance due to New Jersey tax reform enacted during the fourth quarter of 2018. The fourth quarter of 2018 also includes the immediate recognition of certain effects of share-based compensation, acquisition and integration expenses, amortization of purchased intangibles, unrealized gain on investment in equity securities and the finalization of the U.S. tax reform toll charge on undistributed foreign earnings. Under ASC 605 and excluding these items, the effective tax rate would have been approximately 22% during the quarter.

Income from continuing operations under ASC 606 was $1.3 million. Under ASC 605, Income from continuing operations was $32.3 million, or $0.96 per diluted share, compared to $40.2 million, or $1.20 per diluted share, in the same quarter last year.

Adjusted Income from continuing operations, calculated under ASC 605, to be comparable to the prior year results, and including other adjustments described in the table at the end of this press release, was $48.7 million or $1.44 per share, compared to $42.3 million or $1.26 per share in the same quarter last year.

Capital expenditures were $19.1 million and depreciation and amortization was $13.7 million compared to $13.9 million and $8.8 million, respectively, in the same quarter last year.

Net debt was $204.1 million at the end of the quarter, a decrease of $23.7 million during the quarter primarily driven by cash flows from operations.

As a result of the Halo acquisition in September 2018, and to be in alignment with how the business is managed, the Company’s operating segments were aggregated to form two reportable segments, Active Pharmaceutical Ingredients ("APIs") and Finished Dosage Form ("FDF"). The API segment consists of four operating segments which manufactures APIs. The FDF segment consists of one operating segment which manufactures and develops finished dosage form products.

Fourth Quarter 2018 Operating Results – Active Pharmaceutical Ingredients ("API") segment

Net revenue was $110.9 million under ASC 606. Under ASC 605, net revenue was $189.1 million compared to $182.3 in the same quarter last year, a 3.7% increase. Results under ASC 605 include a 2% unfavorable impact of foreign exchange compared to the fourth quarter of 2017. Higher sales of controlled substances was the primary driver of the increase under ASC 605 compared to the same quarter last year.

Gross profit in the fourth quarter of 2018 was $42.6 million. Under ASC 605, Gross profit would have been $81.8 million compared to $78.9 million in the same quarter last year. Gross margins decreased to 38% from 43% in the same quarter last year. Excluding the impact of the new revenue recognition standard, gross margins would have been 43%.

Selling, general and administrative ("SG&A") expenses were $10.2 million in the fourth quarter 2018, compared to $14.0 million in the same quarter last year. The decrease was mainly due to lower personnel related costs and consulting expenses.

Operating profit was $29.3 million under ASC 606 in the fourth quarter 2018. Under ASC 605, operating profit was $68.6 million compared to $61.9 in the fourth quarter 2017. The increase in operating profit under ASC 605 was due to higher gross profit and lower operating expenses.

Fourth Quarter 2018 Operating Results – Finished Dosage Form ("FDF") segment

Results on an ASC 605 basis were not materially different than the reported results under ASC 606.

FDF Net revenue in the fourth quarter of 2018 was $23.4 million under ASC 606.

Gross profit was $5.7 million and gross margin was 24% under ASC 606 in the fourth quarter of 2018.

Selling, general and administrative expenses were $5.4 million in the fourth quarter of 2018 including amortization of purchased intangibles of $3.0 million.

Acquisition and Integration expenses of $1.1 million for the fourth quarter of 2018 represent costs associated with the acquisitions of Halo and Avista.

Operating loss under ASC 606 was $0.7 million. Operating loss includes $1.1 million in integration costs and approximately $3.3 million of increased depreciation and amortization expense resulting from the application of purchase accounting.

Fourth Quarter 2018 Operating Results – Corporate Headquarters

Selling, general and administrative expenses were $5.9 million in the fourth quarter of 2018 compared to $4.3 million in the same quarter last year. The increase is primarily related to higher personnel related expenses.

Acquisition and Integration expenses of $2.3 million for the fourth quarter of 2018 represent costs associated with the acquisitions of Halo and Avista.

Operating loss in the fourth quarter 2018 was $8.8 million compared to $5.6 million in the same quarter last year.

Financial Expectations – Continuing Operations

The following table shows the Company’s current expectations for its full year 2019 financial performance. The expectations in the table below reflect expected results from the business including the recent acquisitions of Halo and Avista. All expectations for 2019, including growth relative to 2018, are based on actual and expected ASC 606 results for both years.

Consistent with the Company’s usual guidance practices, these financial expectations are for continuing operations and exclude the impact of any potential future acquisitions and related transaction and integration expenses, including those related to the recent acquisitions of Halo Pharma and Avista Pharma Solutions, divestitures, restructuring activities, certain tax items discussed below, and the impact of foreign currency on Net revenue.

EBITDA, Adjusted EBITDA and Adjusted Income from continuing operations per share for 2019 will be computed on a basis consistent with the reconciliation of the current quarter financial results in the tables at the end of this press release, except that all 2019 results will be on an ASC 606 basis. Free cash flow is defined as the change in debt, net of cash during the year. Adjusted effective tax rate excludes the immediate recognition of certain benefits of share-based compensation and certain other items adjusted for in the non-GAAP reconciliation tables at the end of this release.

The tax rate will be sensitive to the Company’s geographic mix of income, changes in the tax laws or rates within the countries in which the Company operates and the effects of certain share-based payments. Reconciliations of these measures to measures calculated in accordance with GAAP are not available without unreasonable effort due to the unavailability of certain information needed to calculate certain reconciling items, including interest expense and income tax expense.

We expect M&A and related integration expenses for 2019 to be between $9 and $11 million. These amounts are excluded from our consolidated Adjusted EBITDA and Adjusted income from continuing operations per share guidance included above. These expenses consist of approximately $4.5 million of transaction expenses paid in conjunction with our acquisition of Avista in early January and the remainder will consist of integration expenses incurred across most functional areas throughout 2019. This estimate also includes certain immediate and one-time expenses related to IT systems, but does not include costs to upgrade the two newly acquired businesses to SAP, our ERP software, which will likely happen over the course of 2019 and 2020.

Expectations above include preliminary estimates for Depreciation expense associated with purchase accounting for the Avista acquisition. We expect to finalize the purchase accounting for Avista during the first half of 2019. As a result, expected Depreciation expense and its impact on expected Adjusted Income from continuing operations per share in the table below will likely change when purchase accounting is finalized.

Refer to the tables at the end of this press release which includes items typically adjusted to arrive at the Company’s non-GAAP results.

The financial information contained in this press release is unaudited, subject to revision and should not be considered final until the Company’s 2018 Form 10-K is filed with the SEC.

Conference Call and Webcast

A conference call to discuss the Company’s fourth quarter and full year 2018 results will begin at 8:30 a.m. Eastern Time on February 13, 2019 and can be accessed by calling 1-877-260-1479 for domestic and +1-334-323-0522 for international. Please use the passcode 2955208 and call approximately 10 minutes prior to the start time. A webcast will be available in the Investors section on the Cambrex website located at www.cambrex.com. A telephone replay of the conference call will be available through February 20, 2019 by calling 1-888-203-1112 for domestic and +1-719-457-0820 for international. Please use the passcode 2955208 to access the replay.

Puma Biotechnology to Host Conference Call to Discuss Fourth Quarter and Full Year Financial Results

On February 13, 2019 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported that it will host a conference call at 1:30 p.m. PST/4:30 p.m. EST on Thursday, February 28, 2019 following release of its fourth quarter and full year 2018 financial results (Press release, Puma Biotechnology, FEB 13, 2019, https://investor.pumabiotechnology.com/press-release/puma-biotechnology-host-conference-call-discuss-fourth-quarter-and-full-year-financi-0 [SID1234533273]).

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The call may be accessed by dialing 1-877-709-8150 (domestic) or 1-201-689-8354 (international). Please dial in at least ten minutes in advance and inform the operator that you would like to join the "Puma Biotechnology Conference Call." A live webcast of the conference call and presentation slides may be accessed on the Investors section of the Puma Biotechnology website at View Source A replay of the call will be available approximately one hour after completion of the call and will be archived on Puma’s website for 90 days.

Teva Reports Fourth Quarter and Full Year 2018 Financial Results

On February 13, 2019 Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) reported results for the year and the quarter ended December 31, 2018 (Press release, Teva, FEB 13, 2019, View Source [SID1234533269]).

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Mr. Kåre Schultz, Teva’s President and CEO, said, "2018 was the first year of our restructuring plan and we have met or exceeded all of our key financial targets for the year. The full year yielded a cost base reduction of $2.2 billion, exceeding our 2018 target, and we are well on track to deliver the total $3.0 billion reduction in 2019 as compared to the 2017 spend base. AJOVY is performing very well since its September launch in the U.S. with growing demand for the first and only anti-CGRP treatment with both quarterly and monthly dosing for the preventive treatment of migraine in adults. We will focus our investments on growing AJOVY and continuing our success with AUSTEDO, with both franchises positioned to be important growth drivers for Teva.

"Looking ahead, we continue to expect that 2019 will be the trough for our business, a year in which we will experience similar challenges to those of 2018 including the continued erosion of COPAXONE in the U.S. and Europe as well as the introduction of generics in the ProAir market. Throughout the year, we will continue to execute against our restructuring plan goals, including the optimization of our global portfolio and network, as we focus our efforts on generating cash to reduce the company’s debt."

2018 Annual Consolidated Results

Revenues in 2018 were $18,854 million, a decrease of 16% in both U.S. dollar and local currency terms, compared to 2017, mainly due to generic competition to COPAXONE, a decline in revenues in our U.S. generics business and loss of revenues following the divestment of certain products and discontinuation of certain activities.

Exchange rate movements between 2018 and 2017 positively impacted our revenues by $152 million, our GAAP operating income by $4 million and our non-GAAP operating income by $10 million.

GAAP gross profit was $8,296 million in 2018, a decrease of 22% compared to 2017. GAAP gross profit margin for 2018 was 44.0%, compared to 47.4% in 2017. Non-GAAP gross profit was $9,546 million in 2018, a decrease of 21% compared to 2017. Non-GAAP gross profit margin was 50.6% in 2018, compared to 53.8% in 2017. The decrease in both GAAP and non-GAAP gross profit was mainly due to lower profitability in North America resulting from a decline in COPAXONE revenues due to generic competition and a decline in revenues in our U.S. generics business, partially offset by higher profitability in Europe.

Research and Development (R&D) expenses in 2018 were $1,213 million, a decrease of 32% compared to 2017. R&D expenses excluding equity compensation expenses and purchase of in-process R&D in 2018 were $1,102 million, or 5.8% of revenues, compared to $1,515 million or 6.8% in 2017. The decrease in R&D expenses resulted primarily from pipeline optimization, phase 3 studies that have ended and related headcount reductions.

Selling and Marketing (S&M) expenses in 2018 were $2,916 million, a decrease of 14% compared to 2017. S&M expenses excluding amortization of purchased intangible assets and equity compensation expenses were $2,718 million, or 14.4% of revenues, in 2018, compared to $3,149 million, or 14.1% of revenues, in 2017. The decrease was mainly due to cost reductions and efficiency measures as part of the restructuring plan.

General and Administrative (G&A) expenses in 2018 were $1,298 million, a decrease of 11% compared to 2017. G&A expenses excluding equity compensation expenses were $1,228 million in 2018, or 6.5% of revenues, compared to $1,413 million or 6.3% of revenues in 2017. The decrease was mainly due to cost reductions and efficiency measures as part of the restructuring plan.

GAAP other income in 2018 was $291 million, compared to other income of $1,199 million in 2017. The decline in GAAP other income was primarily the result of none recurring income related to the divestment of our women’s health business in 2017. Non-GAAP other income in 2018 was $225 million, an increase of 94% compared to $116 million in 2017, mainly due to higher Section 8 recoveries from multiple cases in Canada and recovery of lost profits in cases in which U.S. patent infringement litigation had previously prevented the sale of certain products.

GAAP Operating loss was $1,637 million in 2018 compared to operating loss of $17,484 million in 2017. The increase was mainly due higher goodwill impairment charges, higher intangible assets impairments and other asset impairments recorded in 2017. Non-GAAP operating income was $4,723 million, a decrease of 22% compared to $6,073 million in 2017.

Adjusted EBITDA (non-GAAP operating income, which excludes amortization and certain other items, and excluding depreciation expenses) in 2018 was $5,319 million, compared to $6,665 million in 2017.

In 2018, GAAP financial expenses were $959 million, compared to $895 million in 2017. Non-GAAP financial expenses were $893 in 2018, compared to $908 in 2017.

In 2018 we recognized a GAAP tax benefit of $195 million, or 8%, on pre-tax loss of $2,596 million. In 2017 we recognized a tax benefit of $1,933 million, or 11%, on pre-tax loss of $18,379 million. Our tax rate for 2018 was mainly affected by one-time legal settlements and divestments that had a low corresponding tax effect. Additionally, in 2018 we recorded impairments, some of which did not have a corresponding tax effect.

The non-GAAP income taxes for 2018 were $519 million on non-GAAP pre-tax income of $3,830 million. The non-GAAP income taxes in 2017 were $788 million on non-GAAP pre-tax income of $5,165 million. The non-GAAP tax rate for 2018 was 14%, compared to 15% in 2017. The decrease in our tax rate was mainly due to the reduction in the U.S. federal corporate tax rate following the U.S. tax reform.

GAAP net loss attributable to Teva’s ordinary shareholders and GAAP diluted loss per share in 2018 were $2,399 million and $2.35, respectively, compared to net loss of $16,525 million and diluted loss per share of $16.26 in 2017. Non-GAAP net income attributable to ordinary shareholders for calculating diluted EPS and non-GAAP diluted EPS in 2018 were $2,985 million and $2.92, respectively, compared to $4,075 million and $4.01 in 2017.

The weighted average diluted shares outstanding used for the fully diluted share calculation on a GAAP basis for 2018 and 2017 were 1,021 and 1,016 million shares, respectively. The weighted average outstanding shares used for the fully diluted EPS calculation on a non-GAAP basis for 2018 and 2017 were 1,024 and 1,018 million shares, respectively.

As of December 31, 2018 and 2017, the fully diluted share count for purposes of calculating our market capitalization was approximately 1,100 million and 1,086 million shares, respectively.

Non-GAAP information: Net non-GAAP adjustments in 2018 were $5,384 million. Non-GAAP net income and non-GAAP EPS for the year were adjusted to exclude the following items:

A goodwill impairment of $3,027 million, mainly related to International Markets;
An impairment of intangible and fixed assets and equity investment of $2,594 million mainly related to the acquisition of Actavis Generics;
Amortization of purchased intangible assets totaling $1,166 million, of which $1,004 million is included in cost of goods sold and the remaining $162 million in selling and marketing expenses;
Restructuring expenses of $488 million;
Equity compensation expenses of $152 million;
In-Process R&D of $83 million;
Financial expenses of $66 million mainly related to early redemption fees;
Contingent consideration of $57 million;
Other non-GAAP items of $104 million;
Minority interest adjustment of $431 million mainly relate to business venture in International markets;
Related tax effect of $714 million; and
Benefits from legal settlements and loss contingencies of $1,208 million, mainly related to the Allergan working capital adjustments, the Rimsa settlement and the reversal of the reserve recorded for the carvedilol judgement against Teva.
Teva believes that excluding such items facilitates investors’ understanding of its business. For further information see the below tables for a reconciliation of the U.S. GAAP results to the adjusted non-GAAP figures and the information under "Non-GAAP Financial Measures." Investors should consider non-GAAP financial measures in addition to, and not as replacement for, or superior to, measures of financial performance prepared in accordance with GAAP.

Cash flow generated from operating activities in 2018 was $2,446 million, an increase of $221 million, or 10% compared to 2017. This increase was mainly due to the working capital adjustment with Allergan and the Rimsa settlement in 2018, partially offset by lower profit in our North America segment.

Free cash flow (Cash flow generated from operating activities in 2018, net of cash used for capital investments and beneficial interest collected in exchange for securitized trade receivables) was $3,679 million, compared to $2,693 million in 2017. This increase resulted mainly from the higher cash flow generated from operating activities, higher beneficial interest collected in exchange for securitized trade receivables and lower capital expenditures.

As of December 31, 2018, our debt was $28,916 million, compared to $32,475 million as of December 31, 2017. The decrease was mainly due to senior notes and term loans repaid at maturity or prepaid with cash generated during the year. The portion of total debt classified as short-term as of December 31, 2018 was 8%, compared to 11% as of December 31, 2017, due to a decrease in current maturities. Our average debt maturity was approximately 6.8 years as of December 31, 2018, compared to 6.4 years as of December 31, 2017.

Annual Report on Form 10-K

Teva will file its Annual Report on Form 10-K with the SEC in the coming days. The report will include a complete analysis of the financial results for 2018 and will be available on Teva’s website, View Source, as well as on the SEC’s website: View Source

Fourth Quarter 2018 Consolidated Results

Revenues in the fourth quarter of 2018 were $4,559 million, a decrease of 16%, or 14% in local currency terms, compared to the fourth quarter of 2017, mainly due to generic competition to COPAXONE, a decline in revenues in our U.S. generics business and loss of revenues following the divestment of certain products and discontinuation of certain activities.

Exchange rate differences between the fourth quarter of 2018 and the fourth quarter of 2017 negatively impacted our revenues and GAAP operating income by $100 million and $13 million, respectively. Our non-GAAP operating income was negatively impacted by $17 million.

GAAP gross profit was $1,971 million in the fourth quarter of 2018, a decrease of 19% compared to the fourth quarter of 2017. GAAP gross profit margin was 43.2% in the fourth quarter of 2018, compared to 45.3% in the fourth quarter of 2017. Non-GAAP gross profit was $2,328 million in the fourth quarter of 2018, a decline of 15% from the fourth quarter of 2017. Non-GAAP gross profit margin was 51.1% in the fourth quarter of 2018, compared to 50.9% in the fourth quarter of 2017. The increase in gross profit margin on a non-GAAP basis resulted primarily from improved gross profit margin in our Europe segment.

Research and Development (R&D) expenses for the fourth quarter of 2018 were $295 million, a decrease of 15% compared to the fourth quarter of 2017. R&D expenses excluding equity compensation expenses and other expenses were $289 million, or 6.3% of quarterly revenues in the fourth quarter of 2018, compared to $295 million, or 5.5% of quarterly revenues in the fourth quarter of 2017. The decrease in R&D expenses resulted primarily from pipeline optimization, phase 3 studies that have ended and related headcount reduction.

Selling and Marketing (S&M) expenses in the fourth quarter of 2018 were $797 million, a decrease of 3% compared to the fourth quarter of 2017. S&M expenses excluding amortization of purchased intangible assets, equity compensation expenses and other expenses were $768 million, or 16.8% of quarterly revenues in the fourth quarter of 2018, compared to $749 million, or 13.9% of quarterly revenues in the fourth quarter of 2017. The increase was mainly due to higher promotional cost associated with the launch of AJOVY in the U.S., partially offset by cost reduction and efficiency measures as part of the restructuring plan.

General and Administrative (G&A) expenses in the fourth quarter of 2018 were $344 million, a decrease of 2% compared to the fourth quarter of 2017. G&A expenses excluding equity compensation expenses and other expenses were $330 million in the fourth quarter of 2018, or 7.2% of quarterly revenues in the fourth quarter of 2018, compared to $335 million, or 6.2% of quarterly revenues in the fourth quarter of 2017.

GAAP other loss in the fourth quarter of 2018 was $43 million, compared to other income of $1,099 million in the fourth quarter of 2017. Non-GAAP other income in the fourth quarter of 2018 was $5 million, compared to $15 million in fourth quarter of 2017.

GAAP operating loss in the fourth quarter of 2018 was $3,164 million, compared to $13,017 million in the fourth quarter of 2017. Non-GAAP operating income in the fourth quarter of 2018 was $946 million, a decrease of 32% compared to the fourth quarter of 2017. Non-GAAP operating margin was 20.8% in the fourth quarter of 2018 compared to 25.7% in the fourth quarter of 2017.

EBITDA (non-GAAP operating income, which excludes amortization and certain other items, as well as depreciation expenses) was $1,091 million in the fourth quarter of 2018, a decrease of 29% compared to $1,534 million in the fourth quarter of 2017.

GAAP financial expenses for the fourth quarter of 2018 were $223, compared to $191 million in the fourth quarter of 2017. Non-GAAP financial expenses were $216 million in the fourth quarter of 2018, compared to $209 million in the fourth quarter of 2017.

In the fourth quarter of 2018, we recognized a tax benefit of $139 million, or 4%, on pre-tax loss of $3,387 million. In the fourth quarter of 2017, we recognized a tax benefit of $1,471 million, on pre-tax loss of $13,208 million. Our tax rate for the fourth quarter of 2018 was mainly affected by impairments recorded, some of which did not have a corresponding tax effect. Non-GAAP income taxes for the fourth quarter of 2018 were $96 million, or 13%, on pre-tax non-GAAP income of $730 million. Non-GAAP income taxes in the fourth quarter of 2017 were $183 million, or 16%, on pre-tax non-GAAP income of $1,176 million.

GAAP net loss attributable to ordinary shareholders and GAAP diluted loss per share in the fourth quarter of 2018 were $2,940 million and $2.85, respectively, compared to loss of $11,600 million and $11.41 in the fourth quarter of 2017. Non-GAAP net income attributable to ordinary shareholders and non-GAAP diluted EPS in the fourth quarter of 2018 were $543 million and $0.53, respectively, compared to $949 million and $0.93 in the fourth quarter of 2017.

For the fourth quarter of 2018, the weighted average outstanding shares for the fully diluted EPS calculation on a GAAP basis was 1,031 million shares, compared to 1,017 million shares in the fourth quarter of 2017. The weighted average outstanding shares for the fully diluted EPS calculation on a non-GAAP basis was 1,034 million shares, compared to 1,018 million shares in the fourth quarter of 2017.

Non-GAAP information: Net non-GAAP adjustments in the fourth quarter of 2018 were $3,483 million. Non-GAAP net income and non-GAAP EPS for the fourth quarter were adjusted to exclude the following items:

A goodwill impairment of $2,727 million, mainly related to International Markets;
An impairment of intangible and fixed assets and equity investment of $990 million mainly related to the acquisition of Actavis Generics;
Amortization of purchased intangible assets totaling $257 million, of which $233 million is included in cost of goods sold and the remaining $24 million in selling and marketing expenses;
Restructuring expenses of $46 million;
Legal settlements and loss contingencies of $31 million;
Equity compensation expenses of $30 million;
Other non-GAAP items of $36 million;
Minority interest adjustment of $399 million related to business venture in the International markets; and
Related tax effect of $235 million.
Teva believes that excluding such items facilitates investors’ understanding of its business. See the attached tables for a reconciliation of the GAAP results to the adjusted non-GAAP figures. Investors should consider non-GAAP financial measures in addition to, and not as replacement for, or superior to, measures of financial performance prepared in accordance with GAAP.

Cash flow generated from operations during the fourth quarter of 2018 was $367 million, compared to $859 million in the fourth quarter of 2017. The decrease was mainly due to lower profit in our North America segment.

Free cash flow (Cash flow generated from operating activities, net of cash used for capital investments and beneficial interest collected in exchange for securitized trade receivables) was $522 million in the fourth quarter of 2018, compared to $934 million in the fourth quarter of 2017. The increase in 2018 resulted mainly from the higher cash flow generated from operating activities.

Segment Results for the Fourth Quarter 2018

Due to the organizational changes announced in November 2017, we began reporting our financial results under a new structure in the first quarter of 2018, consisting of the following segments:

a) North America segment, which includes the United States and Canada.
b) Europe segment, which includes the European Union and certain other European countries.
c) International Markets segment, which includes all countries other than those in our North America and Europe segments.

In addition to these three segments, we have other activities, primarily the sale of API to third parties and certain contract manufacturing services.

Segment profit is comprised of gross profit for the segment, less R&D, S&M, G&A expenses and other income related to each segment. Segment profit does not include amortization and certain other items.

The data presented in this press release for prior periods have been conformed to reflect our current segment reporting, which commenced in the first quarter of 2018.

North America Segment

Our North America segment includes the United States and Canada.

Revenues from our North America segment in the fourth quarter of 2018 were $2,238 million, a decrease of $451 million, or 17%, compared to the fourth quarter of 2017, mainly due to a decline in revenues of COPAXONE, our U.S. generics business, ProAir and QVAR and the loss of revenues from the sale of our women’s health business, partially offset by higher revenues from AUSTEDO and Anda.

Revenues in the United States, our largest market, were $2,103 million in the fourth quarter of 2018, a decrease of $434 million, or 17%, compared to the fourth quarter of 2017.

Revenues by Major Products and Activities

Generic products revenues in our North America segment in the fourth quarter of 2018 decreased by 10% to $1,099 million, compared to the fourth quarter of 2017, mainly due to additional competition to methylphenidate extended-release tablets (Concerta authorized generic), portfolio optimization primarily as part of the restructuring plan as well as market dynamics and price erosion in our U.S. generics business, partially offset by new generic product launches.

In the fourth quarter of 2018, we led the U.S. generics market in total prescriptions and new prescriptions, with approximately 504 million total prescriptions (based on trailing twelve months), representing 13% of total U.S. generic prescriptions according to IQVIA data.

COPAXONE revenues in our North America segment in the fourth quarter of 2018 decreased by 44% to $356 million, of which $341 million were generated in the United States, compared to the fourth quarter of 2017, mainly due to generic competition in the United States.

BENDEKA and TREANDA combined revenues in our North America segment in the fourth quarter of 2018 decreased by 11% to $140 million, compared to the fourth quarter of 2017, mainly due to lower volumes resulting from Eagle Pharmaceuticals’ launch of a ready-to-dilute bendamustine hydrochloride in June 2018, partially offset by higher pricing.

ProAir revenues in our North America segment in the fourth quarter of 2018 decreased by 56% to $45 million, compared to the fourth quarter of 2017, mainly due to higher sales reserves recorded in the fourth quarter of 2018 in anticipation of generic competition to the short-acting beta-agonist class of drugs, including an approved generic version of Ventolin HFA. In the albuterol inhaler category, approximately 40% of prescriptions are written as "generic albuterol," which means that the launch of any generic inhaler may cause patient migration to such generic products. We launched our own ProAir authorized generic in the United States in January 2019.

QVAR revenues in our North America segment in the fourth quarter of 2018 decreased by 81% to $9 million, compared to the fourth quarter of 2017. The decrease in sales was mainly due to lower net pricing.

AUSTEDO revenues in our North America segment in the fourth quarter of 2018 were $68 million, compared to $17 million in the fourth quarter of 2017.

Anda revenues in our North America segment in the fourth quarter of 2018 increased by 26% to $363 million, compared to the fourth quarter of 2017.

North America Gross Profit

Gross profit from our North America segment in the fourth quarter of 2018 was $1,201 million, a decrease of 20% compared to $1,506 million in the fourth quarter of 2017. The decrease was mainly due to lower revenues from COPAXONE and generic products.

Gross profit margin for our North America segment in the fourth quarter of 2018 decreased to 53.7%, compared to 56.0% in the fourth quarter of 2017. This decrease was mainly due to lower COPAXONE revenues.

North America Profit

Profit from our North America segment in the fourth quarter of 2018 was $551 million, a decrease of 41% compared to $938 million in the fourth quarter of 2017. The decrease was mainly due to lower revenues from COPAXONE and generic products as well as investment in the launch of AJOVY.

Europe Segment

Our Europe segment includes the European Union and certain other European countries.

The following table presents revenues, expenses and profit for our Europe segment for the three months ended December 31, 2018 and 2017:

Revenues from our Europe segment in the fourth quarter of 2018 were $1,204 million, a decrease of $246 million, or 17%, compared to the fourth quarter of 2017. In local currency terms, revenues decreased by 14%, mainly due to the loss of revenues from the closure of our distribution business in Hungary, the sale of our women’s health business and a decline in COPAXONE revenues, partially offset by new generic product launches.

Revenues by Major Products and Activities

The following table presents revenues for our Europe segment by major products and activities for the three months ended December 31, 2018 and 2017:

Generic products revenues in our Europe segment in the fourth quarter of 2018, including OTC products, decreased by 9% to $844 million, compared to the fourth quarter of 2017. In local currency terms, revenues decreased by 6%, mainly due to the loss of revenues from the termination of the PGT joint venture and generic price reductions, partially offset by new generic product launches.

COPAXONE revenues in our Europe segment in the fourth quarter of 2018 decreased by 24% to $118 million, compared to the fourth quarter of 2017. In local currency terms, revenues decreased by 21%, mainly due to price reductions resulting from the entry of competing glatiramer acetate products.

Respiratory products revenues in our Europe segment in the fourth quarter of 2018 decreased by 18% to $90 million, compared to the fourth quarter of 2017. In local currency terms, revenues decreased by 15%, mainly due to lower sales in the United Kingdom.

Europe Gross Profit

Gross profit from our Europe segment in the fourth quarter of 2018 was $689 million, a decrease of 9% compared to $758 million in the fourth quarter of 2017. The decrease was mainly due to the loss of revenues from the sale of our women’s health business and a decline in COPAXONE revenues. Gross profit margin for our Europe segment in the fourth quarter of 2018 increased to 57.2%, compared to 52.3% in the fourth quarter of 2017. This increase was mainly due to lower cost of goods sold, primarily as a result of the termination of the PGT joint venture and the closure of our distribution business in Hungary.

Europe Profit

Profit from our Europe segment in the fourth quarter of 2018 was $253 million, a decrease of 16% compared to $301 million in the fourth quarter of 2017. The decrease was mainly due to lower revenues, partially offset by cost reductions and efficiency measures as part of the restructuring plan.

International Markets Segment

Our International Markets segment includes all countries other than those in our North America and Europe segments. The key markets in this segment are Japan, Israel and Russia.

During the fourth quarter of 2017, we deconsolidated our subsidiaries in Venezuela from our financial results. Consequently, results of operations of our subsidiaries in Venezuela are not included in the fourth quarter of 2018.

The following table presents revenues, expenses and profit for our International Markets segment for the three months ended December 31, 2018 and 2017:

Revenues from our International Markets segment in the fourth quarter of 2018 were $740 million, a decrease of $170 million, or 19%, compared to the fourth quarter of 2017. In local currency terms, revenues decreased 13% compared to the fourth quarter of 2017, mainly due to lower sales in Russia and Japan, the effect of the deconsolidation of our subsidiaries in Venezuela and the loss of revenues from the sale of our women’s health business.

Revenues by Major Products and Activities

The following table presents revenues for our International Markets segment by major products and activities for the three months ended December 31, 2018 and 2017:

Generic products revenues in our International Markets segment in the fourth quarter of 2018, which include OTC products, decreased by 23% to $499 million, compared to the fourth quarter of 2017. In local currency terms, revenues decreased by 18%, mainly due to lower sales in Russia and lower sales in Japan resulting from regulatory pricing reductions and generic competition to off-patented products.

COPAXONE revenues in our International Markets segment in the fourth quarter of 2018 decreased by 23% to $20 million, compared to the fourth quarter of 2017. In local currency terms, revenues decreased by 6%.

Distribution revenues in our International Markets segment in the fourth quarter of 2018 increased by 1% to $146 million, compared to the fourth quarter of 2017. In local currency terms, revenues increased by 6%.

International Markets Gross Profit

Gross profit from our International Markets segment in the fourth quarter of 2018 was $312 million, a decrease of 20% compared to $390 million in the fourth quarter of 2017. Gross profit margin for our International Markets segment in the fourth quarter of 2018 decreased to 42.1%, compared to 42.9% in the fourth quarter of 2017. The decrease was mainly due to lower gross profit resulting from changes in the product mix in certain countries, mainly Russia and Japan.

International Markets Profit

Profit from our International Markets segment in the fourth quarter of 2018 was $114 million, compared to $155 million in the fourth quarter of 2017. The decrease was mainly due to lower revenues in Russia and Japan, partially offset by cost reductions and efficiency measures as part of the restructuring plan.

Other Activities

We have other sources of revenues, primarily the sale of API to third parties and certain contract manufacturing services. These other activities are not included in our North America, Europe or International Markets segments.

Our revenues from other activities in the fourth quarter of 2018 increased by 8% to $377 million, compared to the fourth quarter of 2017. In local currency terms, revenues increased by 9%.

API sales to third parties in the fourth quarter of 2018 were $209 million, an increase of 16% compared to the fourth quarter of 2017. In local currency terms, revenues increased by 16%.

Conference Call

Teva will host a conference call and live webcast along with a slide presentation on Wednesday, February 13, 2019 at 8:00 a.m. ET to discuss its fourth quarter and annual 2018 results and overall business environment. A question & answer session will follow.

passcode: 1174907

A live webcast of the call will also be available on Teva’s website at: ir.tevapharm.com. Please log in at least 10 minutes prior to the conference call in order to download the applicable software.

Following the conclusion of the call, a replay of the webcast will be available within 24 hours on the Company’s website by calling United States 1-866-331-1332; International +44 (0) 3333 009785; passcode: 1174907.

Ascletis and 3-V Biosciences Announce NASH Strategic License and Series E Financing

On February 12, 2019 Ascletis Pharma Inc. (Ascletis, 1672.HK) and 3-V Biosciences, Inc. (3-V Biosciences) jointly reported that Ascletis, through its subsidiary, and 3-V Biosciences have entered into an exclusive license agreement for 3-V Biosciences’ FASN (fatty acid synthase) inhibitor TVB-2640 (Ascletis code: ASC40), a first-in-class, Phase 2-ready drug candidate for non-alcoholic steatohepatitis (NASH), in Greater China (Press release, Ascletis, FEB 12, 2019, View Source [SID1234577322]).

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In conjunction with the license agreement, 3-V Biosciences raised US$18 million in a Series E financing led by new investor Ascletis, through its subsidiary. Ascletis is joined in this financing by new investor Qianhai Ark (Cayman) Investment Co. Limited and existing investors New Enterprise Associates, Inc. (NEA) and Kleiner Perkins (KP). All investors have committed to fund an additional US$7 million in a subsequent financing. 3-V Biosciences expects to use the proceeds of the financing to support the continued development of TVB-2640, including its Phase 2 trials for NASH in the United States and China.

Under the terms of the license agreement, 3-V Biosciences granted Ascletis an exclusive license to develop, manufacture and commercialize ASC40 (TVB-2640) and related compounds in Greater China. 3-V Biosciences is eligible to receive development and commercial milestones as well as tiered royalties on future net sales of ASC40 (TVB-2640).

"We are excited about this strategic collaboration with 3-V Biosciences. Results from the phase 1b trial showed significant decrease in liver fat synthesis and indicate that ASC40 (TVB-2640) may be a promising treatment for NASH," said Jinzi J. Wu, PhD, Founder, Chairman and CEO of Ascletis, "There are no approved therapies today for NASH in China and globally. We’re thrilled to develop ASC40 (TVB-2640) for NASH in Greater China and support 3-V Biosciences’ Phase 2 multi-center trials in the United States and China."

"3-V Biosciences is excited about our partnership with Ascletis; Ascletis brings expertise and capabilities that can accelerate the advancement of TVB-2640 (ASC40) on a global scale for this important emerging disease," said George Kemble, PhD, CEO of 3-V Biosciences.

"The partnership with Ascletis, a leading expert in liver diseases, will accelerate the development of TVB-2640. We are delighted to welcome Dr. Wu to the board, and I look forward to working with him," said Beth Seidenberg, MD, board director of 3-V Biosciences and managing director of KP, an existing shareholder.

According to Dr. Rohit Loomba, MD of Univ. California San Diego, Director, NAFLD Research Center, and Principal Investigator of the upcoming Phase 2 study of TVB-2640, "I am excited to see the advancement of this compound; lipid synthesis is an important driver of NASH. This study will evaluate the impact of TVB-2640 on liver fat using advanced imaging techniques that are expected to predict the ability of this drug to address this unmet medical need."

"In 2016, there were approximately 243 million people in China with non-alcoholic fatty liver disease (NAFLD). By 2030, this is expected to increase to approximately 314 million people, of which 2.3 million will have cirrhosis," said Professor Wei Lai, MD, Director, Peking University Hepatology Institute, Chair, NAFLD and Alcoholic Liver Disease Special Interest Group (ALD SIG), Past-immediate President, Chinese Society of Hepatology of the Chinese Medical Association. "Inhibition of FASN is a promising mechanism of action for NASH. It is encouraging that Chinese biotech takes on the challenge to develop the first-in-class drug for such unmet medical need."

About TVB-2640 (ASC40).

TVB-2640 is an orally bioavailable, first-in-class inhibitor of FASN. FASN is a key enzyme in the de novo lipogenesis (DNL) pathway and catalyzes the biosynthesis of palmitate, which can then undergo further modifications into other fatty acids and complex lipids. Dysregulation of FASN activity is found in a number of different diseases, including liver diseases and cancer. NAFLD and the more advanced disease of NASH can progress to significant liver diseases, including cirrhosis and hepatocellular carcinoma.