On January 31, 2020 Navrogen, Inc., a biopharmaceutical company specialized in developing therapies for cancer and immune-related disorders, reported the opening of its R&D operations at the Cheyney University science center located in Chester County, PA (Press release, Navrogen, JAN 31, 2020, View Source [SID1234553754]). The move enables the company to expand its proprietary Humoral Immuno Oncology (HIO) technology discovery efforts to identify HIO-suppressed cancer types and development of therapeutic agents that can unlock a patient’s immune system to combat their cancer.

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A subset of tumors produce immune checkpoint factors that suppress a patient’s immune response to attack and destroy dysregulated cancer cells. HIO-suppressed cancers produce proteins, called HIO-factors, that suppress antibody-mediated "humoral" immune responses that are generated by a patient’s immune system to attack dysregulated cancer cells. These factors can suppress antibody-mediated tumor cell killing of those generated by a patient’s humoral immune response as well as antibody-based drugs including Rituxan in non-Hodgkin’s Lymphoma and Herceptin in metastatic breast cancer. Navrogen’s mission focuses on therapeutic solutions to reverse HIO suppression through proprietary screening platforms to identify tumor produced HIO-factors as well as develop therapeutic agents that can overcome a HIO-factor’s immuno-suppressive effect.

"The move to Cheyney enables us to transition to the next phase of our strategic growth plan as we continue to advance the development of our technology platforms and experimental therapies to identify and combat HIO-suppressed cancer types," stated Nicholas Nicolaides, Ph.D., Chief Executive Officer at Navrogen. "As part of the relationship with Cheyney, we will teach students the concepts of cancer immunity and provide them first-hand training in biomedical research to support the University’s mission of bringing unique experiential learning to their students as the company leverages the use of Cheyney’s state-of-the-art research facility and operational maintenance."

On January 31, 2020 Oncotarget reported Intratumoral injection of SD-101 induces significant anti-tumor immunity in preclinical and clinical studies, especially when combined with PD-1 blockade (Press release, Oncotarget, JAN 31, 2020, View Source [SID1234553748]).

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Combination therapy generated CD8+ T cell dependent immunity leading to rejection of both non-injected and injected tumors and long-term survival, even in very large tumors.

Dr. Mary J. Janatpour from Dynavax Technologies, Inc., Emeryville, CA 94608,USA said, "It has long been appreciated by cancer researchers that the phenotypic heterogeneity and progressive evolution of malignant tumors minimizes the chance that any agent targeting a single molecular pathway could effectively cure advanced cancer."

The authors have previously demonstrated in mouse tumor models that employing the innate immune system to prime a T cell response, in combination with checkpoint blockade, results in deep and durable anti-tumor efficacy.

These high response rates were observed in both injected and non-injected tumor lesions and patients with PD-L1 negative tumors, indicating low levels of basal immune inflammation, responded as well as patients with PD-L1 positive tumors.

Intratumorally administered SD-101 exerts its priming activity and ultimate orchestration of a systemic anti-tumor T cell response through multiple mechanisms.

The production of interferon stimulates tumor cell killing by natural killer cells, with ensuing tumor antigen release, and induces chemokines that attract T cells back to the tumor bed.

Low-dose cyclophosphamide decreases Tregs. Additional impacted biological activities have been described, such as:

increased interferon production,
induction of immunogenic cell death,
increases in effector T cells, and
increases in functional NK cells,
…likely to be complementary to SD-101 activity by virtue of modulation of the TME. By administering SD-101 locally, rather than systemically, the researchers demonstrate that localized SD-101 injection combined with systemically administered low-dose cyclophosphamide confers an anti-tumor response at non-injected sites.

The Janatpour research Team concluded that, taken together, the intratumoral SD-101 plus low-dose CY combination may complement existing checkpoint blockade therapies in patients to improve efficacy in the clinic and extend the benefits of immunotherapy to more patients.

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%).