On January 31, 2020 OncoArendi Therapeutics reported that funding awarded by NCBR will allow us to launch another R&D project initiating the new deubiquitinase research platform, which will expand OncoArendi’s R&D pipeline of more advanced R&D programs in the chitinase and arginase platforms (Press release, OncoArendi Therapeutics, JAN 31, 2020, View Source [SID1234553747]). The new platform comprises a group of promising biological targets in immuno-oncology allowing us to solidify our expertise in the most attractive and dynamic area of cancer treatment. The aim of the funded project is to develop a new, anti-cancer drug candidate for immunotherapy of multiple cancers. The competitive advantage of the new experimental drug over currently available therapies will be associated with its unique mechanism of action, safety and efficacy profile, especially when compared to chemotherapy and biologics. Inhibiting deubiquitinase (DUBs) is an innovative therapeutic approach, which complements and expands our expertise developed in the area of ​​arginase inhibitors. It is a natural direction for the growth and expansion of our research pipeline .

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Some deubiquitinase enzymes modulate the level of key proteins in the immune system response to cancer because they regulate the ubiquitination process and subsequent protein degradation. Ubiquitination is an essential process of protein marking for degradation in the organism necessary to activate the cellular "clean-up" system responsible for regulating cell functioning, including multiplication, dying, immune response or antigen presentation. Excessive activity of deubiquitinase can disrupt normal ubiquitination process, which causes many diseases including cancers and neurodegenerative diseases. Inhibiting deubiquitinase hyperactivity restores correct body’s immune response to cancer.

In 2019 OncoArendi carried out pilot exploratory research aimed at blocking the DUBs targets. We were able to develop and validate several new screening assays and counterscreens based on natural deubiquitinase substrates. As a result an early lead structure was identified out of two classes of compounds, which appear to both stimulate the immune response to cancer cells and directly inhibit the proliferation of cancer cells and promote apoptosis. Within the project the company will enter the early lead optimization phase.

On January 31, 2020 IDEXX Laboratories, Inc. (NASDAQ: IDXX), reported revenues of $605 million for the fourth quarter of 2019, an increase of 10% compared to the prior year period on a reported and organic basis (Press release, IDEXX Laboratories, JAN 31, 2020, View Source [SID1234553746]). Fourth quarter results were driven by continued high gains in Companion Animal Group ("CAG") Diagnostics recurring revenue globally, as well as strong growth in the Company’s Water and Livestock, Poultry and Dairy ("LPD") businesses. Earnings per diluted share ("EPS") were $1.04 on a reported basis for the fourth quarter, representing EPS growth of 6% and comparable constant currency EPS growth of 17%, which excludes the impact of CEO transition charges of $0.14 per share. Comparable constant currency growth measures are non-GAAP financial measures and have been modified to exclude operating expense impact of $13 million or $0.14 per share of CEO transition charges as described in our footnotes. Fourth quarter EPS results included $0.05 per share from better than projected share-based compensation tax benefits, $0.04 from lower than projected after-tax CEO transition charges and $0.04 in combined upsides from better than expected effective tax rate and interest expense.

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Revenue for the full year of $2,407 million increased 9% on a reported and 10% on an organic basis, driven by 11% reported and 12% organic growth in CAG Diagnostics recurring revenue. For the full year 2019, EPS of $4.89 increased 15% on a reported basis and 21% on a comparable constant currency basis, supported by a reported 80 basis points of operating margin improvement, or 120 basis points on a comparable constant currency basis.

The Company is maintaining its full year 2020 revenue growth outlook of 9% – 10.5% on a reported and organic basis. The Company is increasing its EPS guidance range to $5.42 – $5.58, an increase of $0.12 per share, reflecting consistent expectations for 50 – 100 basis points of comparable constant currency operating margin improvement. The EPS guidance range improvement reflects approximately $0.05 in combined benefit from favorable updates to expectations for interest expense, shares outstanding and flow through of 2019 operating profit performance, approximately $0.05 per share in incremental benefits from projected share-based compensation tax benefits reflecting recent share prices, and $0.02 in benefit from updated projections for foreign exchange rates impacts.

"IDEXX fourth quarter results provided a strong finish to 2019, enabling us to deliver revenue and comparable constant currency EPS gains aligned with our long-term goals. Our full year results were driven by continued strong 12% organic growth in CAG Diagnostics recurring revenues, which now represent 76% of total IDEXX revenue. We are well positioned to build on this progress in 2020, leveraging our expanded global commercial capability and unique innovations which support continued strong diagnostics market growth driven by the adoption of higher standards of care for pets globally," said Jay Mazelsky, the Company’s President and Chief Executive Officer.

Fourth Quarter Performance Highlights

Companion Animal Group

The Companion Animal Group generated 11% reported and organic revenue growth for the quarter. CAG Diagnostics recurring revenue growth remained strong at 11% reported and organic, net of a modest headwind from fewer equivalent days.

IDEXX VetLab consumables generated 11% reported and 12% organic revenue growth, net of a 1.5% growth headwind from fewer equivalent days. IDEXX VetLab consumable growth was supported by our expanding premium instrument installed base and benefits from diagnostics utilization growth. IDEXX Catalyst instrument placements grew 23% to a record number of 2,517, with the majority of placements at new and competitive accounts.
Reference laboratory diagnostic and consulting services generated 13% reported and 11% organic revenue growth, including nearly 1% of equivalent days benefit. These results were driven by continued low to mid-teen organic growth in the U.S. and consistent high-single-digit international reference lab organic revenue gains.
Rapid assay products generated revenue growth of 4% on a reported and organic basis, net of a 1.5% growth headwind from fewer equivalent days. Rapid assay products growth was supported by continued gains in SNAP 4Dx Plus Tests, specialty and first generation rapid assay test volumes.
Veterinary software services and diagnostic imaging systems revenue growth increased 9% on a reported and organic basis, supported by double-digit growth in veterinary software and services.

Water

Water achieved revenue growth of 9% on a reported basis and 10% on an organic basis, including a 1% growth benefit from greater equivalent days. Water growth was supported by solid gains in the U.S. and strong growth in international markets.

Livestock, Poultry and Dairy ("LPD")

LPD revenue increased 8% on a reported basis and 10% on an organic basis, reflecting favorable comparisons related to year-end government and distributor order timing, gains from African Swine Fever diagnostic testing programs in China and growth in diagnostic testing associated with alternate food sources, such as poultry.

Gross Profit and Operating Profit

Gross profits increased 10%, and gross margins were flat year-over-year at 54.7%. On a constant currency basis, gross margin was slightly lower than fourth quarter 2018, reflecting increased investment in our reference lab business related to day lab capacity, courier route expansion, technology investments and acquisition integration, partially offset by continued solid net price gains and strong growth in consumable revenues.

Operating margin was 19.1% in the quarter, 190 basis points lower than the prior year period results on a reported basis and relatively flat on a comparable constant currency basis. Operating expenses increased 16% on a reported basis, reflecting the impact of the CEO transition charges, and 10% on a comparable constant currency basis, driven by increases in our CAG segment’s sales and marketing costs and research and development spending.

2020 Financial Outlook

The following guidance for 2020 reflects the assumptions that for the remainder of 2020, the value of foreign currencies will remain at the following rates in U.S. dollars:

the euro at $1.10;
the British pound at $1.29;
the Canadian dollar at $0.76; and
the Australian dollar at $0.68;
and relative to the U.S. dollar:

the Japanese yen at ¥110;
the Chinese renminbi at RMB 7.10; and
the Brazilian real at R$4.14.
Outlook for 2020

The Company is raising its 2020 revenue outlook to $2,620 million – $2,655 million, supported by consistent outlook for reported and organic revenue growth of 9% – 10.5%, reflecting expectations for CAG Diagnostics recurring reported and organic revenue growth of 11% – 12%. Updated foreign exchange rate assumptions increased revenue guidance by approximately $5 million. At the foreign exchange rate assumptions in 2020 noted above, we estimate that the effect of the stronger U.S. dollar will reduce full year 2020 reported revenue growth by approximately 0.5%, EPS growth by approximately 2%, and EPS by an estimated $0.09 per share, including the net impact of lower projected hedge gains of approximately $5 million in 2020.

The Company is increasing its 2020 EPS outlook to $5.42 – $5.58 per share, an increase of $0.12 per share, or targeted growth of 11% – 14% on a reported basis and 13% – 16% on a comparable constant currency basis, which excludes a 3% growth rate benefit from comparisons to the 2019 CEO transition charges. The Company is projecting free cash flow at approximately 75% – 80% of net income in 2020, including approximately 7% impact related to $35 million of major facility capital spending for the completion of our Westbrook, Maine headquarters expansion, the relocation and expansion of our core laboratory in Germany, and the acquisition of real estate associated with a leased U.S. reference lab facility. Spending for major facility projects was $58 million in 2019, lower than earlier estimates driven by later timing of cash deployment. For 2020, the Company projects total capital spending, including major projects, of approximately $140 million – $155 million.

The Company provides the following updated guidance for 2020:

Amounts in millions except per share data and percentages

We expect an effective tax rate of 20% – 21%, including expectations for share-based compensation tax benefits of $7.5 million – $9.5 million or approximately 150 basis points. We are now projecting a reduction in weighted average shares outstanding of approximately 1% – 1.5%, and interest expense, net of interest income, of approximately $35 million, reflecting current and projected borrowings.

Conference Call and Webcast Information

IDEXX Laboratories, Inc. will host a conference call today at 8:30 a.m. (Eastern) to discuss its fourth quarter and full year 2019 results and management’s outlook. To participate in the conference call, dial 1-844-767-5679 or 1-409-207-6967 and reference access code 176532. Replay of the conference call will be available through Friday, February 7, 2020 by dialing 1-866-207-1041 or 1-402-970-0847 and referencing replay code 8036553. Individuals can access a live webcast of the conference call through a link on the IDEXX website, www.idexx.com/investors. An archived edition of the webcast will be available after 1:00 p.m. (Eastern) on that day via the same link and will remain available for one year.

On January 31, 2020 Kyowa Kirin, Inc., (Kyowa Kirin, TSE: 4151) reported the final safety data from the MAVORIC (Mogamulizumab anti-CCR4 Antibody Versus ComparatOR In CTCL) trial of mogamulizumab-kpkc, which will be presented at the 12th Annual T-Cell Lymphoma Forum (TCLF) in La Jolla, California (Press release, Kyowa Hakko Kirin, JAN 31, 2020, View Source [SID1234553745]).

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MAVORIC is the first pivotal trial in cutaneous T-cell lymphoma (CTCL) to use progression-free survival (PFS) as a primary endpoint. It is also the largest randomized study to compare systemic therapies in subtypes of CTCL.1 Secondary endpoints included a proportion of patients achieving an overall response rate (ORR), duration of response and safety.1 Primary results were based on a data cutoff of December 31, 2016, which served as the basis of the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) approvals of mogamulizumab for the treatment of the most common subtypes of CTCL as well as a partial change of the product label in Japan.1 The analysis being presented at TCLF reports final safety results of MAVORIC as of the safety data available on January 3, 2019, based on patients who continued participating in the trial post-approval.2

For the final safety analysis, median duration of follow-up was 34.5 months (range, 0.13-70.0).2 Median treatment exposure was 170 days (range, 1-1813) for mogamulizumab and 84 days (4‑1230) for vorinostat, which represent the same median values but broader ranges compared to the primary analysis (primary analysis, 170 days [1-1379] for mogamulizumab and 84 days [4-1058] for vorinostat).2

This final safety analysis from the MAVORIC study in patients with previously treated mycosis fungoides (MF) and Sézary syndrome (SS) demonstrated that mogamulizumab did not identify any new safety signals. The type and frequency of adverse events (AEs) in either the mogamulizumab or vorinostat treatment groups were consistent with those reported in the primary analysis.2 Treatment-emergent adverse events (TEAEs), regardless of causality, were reported at similar rates in the two treatment groups and included constipation, peripheral edema, headache, and anemia.2 TEAEs that occurred at higher frequency in the mogamulizumab vs. vorinostat arm included infusion-related reaction (33.2% vs 0.5%) and drug eruption (25.0% vs 1.1%).2 The majority of these events were grade 1 or 2, and the types and frequencies of AEs attributable to mogamulizumab included infusion-related reaction (33.2% [61/184]), drug eruption (23.9% [44/184]), and fatigue (18.5% [34/184]).2 AEs attributed to vorinostat included diarrhea (55.4% [103/186]), nausea (38.2% [71/186]), and fatigue (33.3% [62/186]).2

In the trial, patients on vorinostat for at least two cycles who demonstrated confirmed disease progression or experienced intolerable toxicity (grade ≥3 adverse events [AEs], excluding inadequately treated nausea, vomiting, and diarrhea; and alopecia), despite dose reduction and appropriate management of side effects, could cross over to treatment with mogamulizumab. This analysis confirmed earlier findings showing that the type and incidence of TEAEs among patients receiving mogamulizumab after crossover were similar to those observed for patients initially randomized to mogamulizumab.2

"We are pleased that this final safety analysis from the MAVORIC study in patients with previously treated MF and SS demonstrates that the additional two years of mogamulizumab safety follow up and treatment exposure did not identify any unexpected safety findings," said Jeffrey S. Humphrey, MD, Chief Development Officer of Kyowa Kirin, Inc.

POTELIGEO (mogamulizumab-kpkc) is approved in the U.S. for the treatment of adult patients with relapsed or refractory MF or SS after at least one prior systemic therapy.3 MF and SS are the most common subtypes of CTCL.4

Please see Poteligeo Indication and Important Safety Information below.

INDICATION
POTELIGEO (mogamulizumab-kpkc) injection, for intravenous infusion is indicated for the treatment of adult patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after at least one prior systemic therapy.

Important Safety Information
Warnings and Precautions:

Dermatologic toxicity: Monitor patients for rash throughout the course of treatment. For patients who experienced dermatologic toxicity in Trial 1, the median time to onset was 15 weeks, with 25% of cases occurring after 31 weeks. Interrupt POTELIGEO for moderate or severe rash (Grades 2 or 3). Permanently discontinue POTELIGEO for life-threatening (Grade 4) rash or for any Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN).
Infusion reactions: Most infusion reactions occur during or shortly after the first infusion. Infusion reactions can also occur with subsequent infusions. Monitor patients closely for signs and symptoms of infusion reactions and interrupt the infusion for any grade reaction and treat promptly. Permanently discontinue POTELIGEO for any life-threatening (Grade 4) infusion reaction.
Infections: Monitor patients for signs and symptoms of infection and treat promptly.
Autoimmune complications: Interrupt or permanently discontinue POTELIGEO as appropriate for suspected immune-mediated adverse reactions. Consider the benefit/risk of POTELIGEO in patients with a history of autoimmune disease.
Complications of allogeneic HSCT after POTELIGEO: Increased risks of transplant complications have been reported in patients who received allogeneic HSCT after POTELIGEO. Follow patients closely for early evidence of transplant-related complications.
Adverse Reactions:

The most common adverse reactions (reported in ≥ 10% of patients) with POTELIGEO in the clinical trial were rash, including drug eruption (35%), infusion reaction (33%), fatigue (31%), diarrhea (28%), drug eruption (24%), upper respiratory tract infection (22%), musculoskeletal pain (22%), skin infection (19%), pyrexia (17%), edema (16%), nausea (16%), headache (14%), thrombocytopenia (14%), constipation (13%), anemia (12%), mucositis (12%), cough (11%), and hypertension (10%).

On January 31, 2020 Pfizer Inc. (NYSE: PFE) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion, recommending marketing authorization for RUXIENCE (rituximab),1 a potential biosimilar to MabThera (rituximab).2,3 RUXIENCE is a monoclonal antibody (mAb) for the treatment of non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), and pemphigus vulgaris (PV) (Press release, Pfizer, JAN 31, 2020, View Source [SID1234553744]).1 The CHMP’s opinion will now be reviewed by the European Commission, with a regulatory decision anticipated in the first half of 2020.

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"Biosimilars like RUXIENCE can play an important role in cancer care, helping to expand patient access to potentially life-changing therapies," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. "We are committed to bringing biosimilars like RUXIENCE to the market as a treatment option with similar safety and efficacy to the originator product at a potentially lower cost. If approved, RUXIENCE would become Pfizer’s fifth oncology biosimilar to receive regulatory approval in Europe."

The regulatory submission is supported by a comprehensive data package which demonstrates biosimilarity of RUXIENCE to the reference product. This includes results from the REFLECTIONS B3281006 clinical comparative study, which evaluated the efficacy, safety and immunogenicity, pharmacokinetics and pharmacodynamics of RUXIENCE and found no clinically meaningful differences in safety or efficacy compared to the reference product in patients with CD20-positive, low tumor burden follicular lymphoma.4

Biosimilars have been a significant catalyst for change for the healthcare industry over the last decade, with the potential to help create a more sustainable healthcare system. With more than 10 years of global in-market experience and five approved biosimilar products in Europe, Pfizer is proud to be a leader and at the forefront of this vital healthcare segment. RUXIENCE was also approved for use in the United States for the treatment of adult patients with NHL, CLL, GPA and MPA in 2019 and was recently made available to U.S. patients.

On January 31, 2020 Seattle Genetics, Inc. (Nasdaq:SGEN) reported that the European Medicines Agency (EMA) validated the Marketing Authorization Application (MAA) for tucatinib, in combination with trastuzumab and capecitabine, for the treatment of adult patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received at least two prior anti-HER2 treatment regimens (Press release, Seattle Genetics, JAN 31, 2020, View Source [SID1234553743]). The EMA validation of the MAA confirms that the submission is sufficiently complete to begin the formal review process. Tucatinib is an oral, small molecule tyrosine kinase inhibitor (TKI) that is highly selective for HER2.

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"Today, we achieved a significant milestone towards our goal of making tucatinib available to patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including those with brain metastases, around the world," said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. "We look forward to working with the EMA throughout the review process. If approved, tucatinib has the potential to be a clinically meaningful advance for patients in this disease setting."

The MAA is based on data from the pivotal HER2CLIMB clinical trial, which compared tucatinib in combination with trastuzumab and capecitabine to trastuzumab and capecitabine alone in patients with locally advanced unresectable or metastatic HER2-positive breast cancer. Patients had previously received trastuzumab, pertuzumab and T-DM1 (ado-trastuzumab emtansine). Patients had received a median of four prior lines of therapy overall and three in the metastatic setting. Forty-seven percent of the patients enrolled in the trial had brain metastases at the time of enrollment. Results of the pivotal HER2CLIMB trial were presented during an oral presentation at the 2019 San Antonio Breast Cancer Symposium (SABCS) and simultaneously published in the New England Journal of Medicine(NEJM).

The New Drug Application (NDA) for tucatinib was submitted to the U.S. Food and Drug Administration (FDA) on December 23, 2019 under the Real-Time Oncology Review Pilot Program. The review of the tucatinib NDA is also being conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among participating international partners. Tucatinib was recently granted Breakthrough Therapy designation by the FDA in combination with trastuzumab and capecitabine, for the treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have been treated with trastuzumab, pertuzumab, and T-DM1. This designation was based on data from the HER2CLIMB trial.

About HER2CLIMB

HER2CLIMB is a multinational randomized (2:1), double-blind, placebo-controlled, active comparator, pivotal clinical trial comparing tucatinib in combination with trastuzumab and capecitabine compared with trastuzumab and capecitabine alone in patients with locally advanced unresectable or metastatic HER2-positive breast cancer who were previously treated with trastuzumab, pertuzumab and T-DM1. The primary endpoint of the trial was progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as determined by blinded independent central review (BICR) in the first 480 patients enrolled in the trial. HER2CLIMB enrolled a total of 612 patients to support the analyses of key secondary endpoints, including overall survival, PFS per BICR in patients with brain metastases at baseline and confirmed objective response rate (ORR). Safety data were evaluated throughout the study.

About HER2-Positive Breast Cancer

Patients with HER2-positive breast cancer have tumors with high levels of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the aggressive spread of cancer cells. An estimated 271,270 new cases of invasive breast cancer will be diagnosed in the U.S. in 2019.1 Between 15 and 20 percent of breast cancer cases worldwide are HER2-positive.2 Historically, HER2-positive breast cancer tends to be more aggressive and more likely to recur than HER2-negative breast cancer.2, 3, 4 In patients with metastatic breast cancer, the most common site of first metastasis is in bone, followed by lung, brain, and liver.5, 6 Up to 50 percent of metastatic HER2-positive breast cancer patients develop brain metastases over time.2, 7 Despite recent treatment advances, there is still a significant need for new therapies that can impact metastatic disease, especially brain metastases. There are currently no approved therapies demonstrating progression-free survival or overall survival benefit for the treatment of patients with HER2-positive metastatic breast cancer after progression on T-DM1.8, 9, 10

About Tucatinib

Tucatinib is an investigational, orally bioavailable, potent tyrosine kinase inhibitor that is highly selective for HER2 without significant inhibition of EGFR. Inhibition of EGFR has been associated with significant toxicities, including skin rash and diarrhea. Tucatinib has shown activity as a single agent and in combination with both chemotherapy and other HER2 targeted agents such as trastuzumab.1,2 Studies of tucatinib in these combinations have shown activity both systemically and in brain metastases. HER2 is a growth factor receptor that is overexpressed in multiple cancers, including breast, colorectal and gastric cancers. HER2 mediates cell growth, differentiation and survival. Tucatinib has been granted orphan drug designation by the FDA for the treatment of breast cancer patients with brain metastases.

In addition to HER2CLIMB, tucatinib is being evaluated in a randomized, double-blind, placebo-controlled, multi-center phase 3 trial of tucatinib in combination with T-DM1 compared to T-DM1 alone, in patients with unresectable locally advanced or metastatic HER2-positive breast cancer, including those with brain metastases, who have had prior treatment with a taxane and trastuzumab. The primary endpoint is PFS per RECIST criteria. Secondary endpoints include overall survival, objective response rate and duration of response. This global trial is expected to enroll approximately 460 patients. More information about the phase 3 trial, including enrolling centers, is available at www.clinicaltrials.gov.

Tucatinib is also being evaluated in a multi-center, open-label, single-arm phase 2 clinical trial known as MOUNTAINEER, which is evaluating tucatinib in combination with trastuzumab in patients with HER2-positive, RAS wildtype metastatic or unresectable colorectal cancer. The primary endpoint of the trial is ORR by RECIST criteria. PFS, duration of response, overall survival and safety and tolerability of the combination regimen are secondary objectives. Results for 26 patients were evaluated in an analysis and presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress. Enrollment is ongoing. More information about the MOUNTAINEER trial, including enrolling centers, is available at www.clinicaltrials.gov.