BioInvent Receives FDA Orphan Designation for BI-1206 for Mantle Cell Lymphoma

On January 30, 2019 BioInvent International AB (OMXS: BINV) reported that the U.S. Food and Drug Administration (FDA) has granted the Company orphan designation for its proprietary antibody BI-1206 for the treatment of mantle cell lymphoma (MCL) (Press release, BioInvent, JAN 30, 2019, View Source [SID1234532964]).

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Orphan designation is intended to support companies developing treatments that target rare medical conditions and are expected to provide significant therapeutic advantage over existing medicines. The orphan designation from the FDA provides certain incentives to BioInvent, including a 7-year market exclusivity in the U.S once a New Drug Application (NDA) or Biologics License Application (BLA) has been approved, and also availability of grants exclusively for orphan drug products.

BioInvent is currently conducting a dose escalation, consecutive-cohort, open-label Phase I/IIa study of BI-1206 with approximately 30 patients across sites in the EU and the U.S. The trial evaluates BI-1206 in combination with rituximab in patients with indolent relapsed or refractory B-cell non-Hodgkin’s lymphoma (NHL). MCL is one of the targeted sub-indications, along with follicular lymphoma (FL) and marginal zone lymphoma (MZL).

"This orphan designation for BI-1206 is very good news for BioInvent, and most importantly for patients suffering from this very serious condition. There is a significant unmet medical need, as there are presently few treatment options for patients suffering from mantle cell lymphoma. We are looking forward to generating data from our Phase I/IIa trial to support the use of BI-1206 in combination with rituximab in this indication," says Martin Welschof, CEO of BioInvent.

Thermo Fisher Scientific Reports Fourth Quarter and Full Year 2018 Results

On January 30, 2019 Thermo Fisher Scientific Inc. (NYSE: TMO), the world leader in serving science, reported its financial results for the fourth quarter and full year ended December 31, 2018 (Press release, Thermo Fisher Scientific, JAN 30, 2019, View Source [SID1234532983]).

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Fourth Quarter and Full Year 2018 Highlights

Fourth quarter revenue grew 8% to $6.51 billion.
Fourth quarter GAAP diluted earnings per share (EPS) increased 71% to $2.22.
Fourth quarter adjusted EPS increased 16% to $3.25.
Full year revenue grew 16% to $24.36 billion.
Full year GAAP diluted EPS increased 30% to $7.24.
Full year adjusted EPS increased 17% to $11.12.
Invested $1 billion in R&D in 2018 and launched a range of new products that strengthened our leading offering, including the Thermo Scientific Vanquish Duo UHPLC system, Thermo Scientific Q Exactive UHMR mass spectrometer, Ion GeneStudio S5 Series next-generation sequencing systems and the Phadia 200 allergy and autoimmune instrument in Europe.
Built on the excellent growth momentum we had all year in Asia-Pacific and Emerging Markets, capped by another very strong quarter in China, where we recently opened our first Bioprocess Design Center to support development of biologics.
Continued to successfully execute our capital deployment strategy in 2018 to create significant shareholder value – reducing debt by $2.0 billion, closing $540 million of bolt-on acquisitions and returning capital through $500 million of stock buybacks and $275 million of dividends.
Adjusted EPS, adjusted operating income, adjusted operating margin and free cash flow are non-GAAP measures that exclude certain items detailed later in this press release under the heading "Use of Non-GAAP Financial Measures."

"I’m pleased to report that we had a very strong finish to the year," said Marc N. Casper, president and chief executive officer of Thermo Fisher Scientific. "Our outstanding performance in 2018 is testament to the success of our growth strategy and great execution by our team.

"In line with our strategy, we continued to innovate to enable our customers’ scientific advances, leveraged our scale in Asia-Pacific and emerging markets to drive growth, and enhanced our customer value proposition with the smooth integration of Patheon. At the same time, we significantly strengthened our balance sheet and effectively deployed our capital by investing in strategic M&A and returning capital to our shareholders."

Casper concluded, "All in all, it was a fantastic year, which puts us in a great position as we begin 2019."

Fourth Quarter 2018

Revenue for the quarter grew 8% to $6.51 billion in 2018, versus $6.05 billion in 2017. Organic revenue growth was 8%; acquisitions increased revenue by 1% and currency translation decreased revenue by 2%. The components of revenue growth do not sum due to rounding.

GAAP Earnings Results
GAAP diluted EPS in the fourth quarter increased 71% to $2.22, versus $1.30 in the same quarter last year. Results in 2017 included a one-time tax provision associated with U.S. tax reform. GAAP operating income for the fourth quarter of 2018 grew to $1.15 billion, compared with $0.96 billion in the fourth quarter of 2017. GAAP operating margin increased to 17.6%, compared with 15.8% in the fourth quarter of 2017.

Non-GAAP Earnings Results
Adjusted EPS in the fourth quarter of 2018 increased 16% to $3.25, versus $2.79 in the fourth quarter of 2017. Adjusted operating income for the fourth quarter of 2018 grew 12% compared with the year-ago quarter. Adjusted operating margin increased 90 basis points to 24.8%, compared with 23.9% in the fourth quarter of 2017.

Full Year 2018

Revenue for the full year grew 16% to $24.36 billion in 2018, versus $20.92 billion in 2017. Organic revenue growth was 8%; acquisitions increased revenue by 7% and currency translation increased revenue by 1%.

GAAP Earnings Results
GAAP diluted EPS for the full year increased 30% to $7.24, versus $5.59 in 2017. Results in 2017 reflect the one-time tax provision noted above. GAAP operating income for 2018 grew to $3.78 billion, compared with $2.96 billion a year ago. GAAP operating margin was 15.5% in 2018, compared with 14.2% in 2017.

Non-GAAP Earnings Results
Adjusted EPS for the full year rose 17% to $11.12, versus $9.49 in 2017. Adjusted operating income for 2018 grew 16% compared with 2017, and adjusted operating margin was 23.1%, compared with 23.2% a year ago.

Annual Guidance for 2019

The company will provide 2019 financial guidance on its earnings conference call this morning at 8:30 a.m. Eastern time.

Segment Results

Management uses adjusted operating results to monitor and evaluate performance of the company’s four business segments, as highlighted below. Since these results are used for this purpose, they are also considered to be prepared in accordance with GAAP.

Life Sciences Solutions Segment

In the fourth quarter of 2018, Life Sciences Solutions Segment revenue grew 8% to $1.70 billion, compared with revenue of $1.58 billion in the fourth quarter of 2017. Segment adjusted operating margin increased to 36.8%, versus 35.5% in the 2017 quarter.

For the full year 2018, Life Sciences Solutions Segment revenue rose 9% to $6.27 billion, compared with revenue of $5.73 billion in 2017. Segment adjusted operating margin increased to 34.4% in 2018, compared with 33.1% a year ago.

Analytical Instruments Segment

Analytical Instruments Segment revenue grew 11% to $1.57 billion in the fourth quarter of 2018, compared with revenue of $1.41 billion in the fourth quarter of 2017. Segment adjusted operating margin increased to 26.6%, versus 24.5% in the 2017 quarter.

For the full year 2018, Analytical Instruments Segment revenue rose 13% to $5.47 billion, compared with revenue of $4.82 billion in 2017. Segment adjusted operating margin grew to 22.8%, versus 21.3% in 2017.

Specialty Diagnostics Segment

In the fourth quarter of 2018, Specialty Diagnostics Segment revenue grew 4% to $0.95 billion, compared with revenue of $0.91 billion in the fourth quarter of 2017. Segment adjusted operating margin was 24.5%, versus 26.4% in the 2017 quarter.

For the full year 2018, Specialty Diagnostics Segment revenue grew 7% to $3.72 billion, compared with revenue of $3.49 billion in 2017. Segment adjusted operating margin was 25.6%, versus 2017 results of 26.6%.

Laboratory Products and Services Segment

Laboratory Products and Services Segment revenue grew 8% to $2.60 billion in the fourth quarter of 2018, compared with revenue of $2.40 billion in the fourth quarter of 2017. Segment adjusted operating margin increased to 13.1%, versus 12.5% in the 2017 quarter.

For the full year 2018, Laboratory Products and Services Segment revenue grew 28% to $10.04 billion, compared with revenue of $7.83 billion in 2017. Segment adjusted operating margin was 12.5%, versus 12.8% in 2017.

Use of Non-GAAP Financial Measures

In addition to the financial measures prepared in accordance with generally accepted accounting principles (GAAP), we use certain non-GAAP financial measures, including adjusted EPS, adjusted operating income and adjusted operating margin, which exclude certain acquisition-related costs, including charges for the sale of inventories revalued at the date of acquisition and significant transaction costs; restructuring and other costs/income; and amortization of acquisition-related intangible assets. Adjusted EPS also excludes certain other gains and losses that are either isolated or cannot be expected to occur again with any predictability, tax provisions/benefits related to the previous items, benefits from tax credit carryforwards, the impact of significant tax audits or events and the results of discontinued operations. We exclude the above items because they are outside of our normal operations and/or, in certain cases, are difficult to forecast accurately for future periods. We also use a non-GAAP measure, free cash flow, which is operating cash flow, excluding net capital expenditures, and also excludes operating cash flows from discontinued operations to provide a view of the continuing operations’ ability to generate cash for use in acquisitions and other investing and financing activities. We believe that the use of non-GAAP measures helps investors to gain a better understanding of our core operating results and future prospects, consistent with how management measures and forecasts the company’s performance, especially when comparing such results to previous periods or forecasts.

For example:

We exclude costs and tax effects associated with restructuring activities, such as reducing overhead and consolidating facilities. We believe that the costs related to these restructuring activities are not indicative of our normal operating costs.

We exclude certain acquisition-related costs, including charges for the sale of inventories revalued at the date of acquisition and significant transaction costs. We exclude these costs because we do not believe they are indicative of our normal operating costs.

We exclude the expense and tax effects associated with the amortization of acquisition-related intangible assets because a significant portion of the purchase price for acquisitions may be allocated to intangible assets that have lives of 3 to 20 years. In 2019, based on acquisitions closed through the end of 2018, our adjusted EPS will exclude approximately $3.27 of expense for the amortization of acquisition-related intangible assets. Exclusion of the amortization expense allows comparisons of operating results that are consistent over time for both our newly acquired and long-held businesses and with both acquisitive and non-acquisitive peer companies.

We also exclude certain gains/losses and related tax effects, benefits from tax credit carryforwards and the impact of significant tax audits or events (such as the effect on deferred tax balances of enacted changes in tax rates or, in 2017, the incremental impact of tax reform legislation in the U.S.), which are either isolated or cannot be expected to occur again with any predictability and that we believe are not indicative of our normal operating gains and losses. For example, we exclude gains/losses from items such as the sale of a business or real estate, gains or losses on significant litigation-related matters, gains on curtailments of pension plans, the early retirement of debt and discontinued operations.

We also report free cash flow, which is operating cash flow, excluding net capital expenditures, and also excludes operating cash flows from discontinued operations to provide a view of the continuing operations’ ability to generate cash for use in acquisitions and other investing and financing activities.

Thermo Fisher’s management uses these non-GAAP measures, in addition to GAAP financial measures, as the basis for measuring the company’s core operating performance and comparing such performance to that of prior periods and to the performance of our competitors. Such measures are also used by management in their financial and operating decision-making and for compensation purposes.

The non-GAAP financial measures of Thermo Fisher’s results of operations and cash flows included in this press release are not meant to be considered superior to or a substitute for Thermo Fisher’s results of operations prepared in accordance with GAAP. Reconciliations of such non-GAAP financial measures to the most directly comparable GAAP financial measures are set forth in the accompanying tables. Thermo Fisher does not provide GAAP financial measures on a forward-looking basis because we are unable to predict with reasonable certainty and without unreasonable effort items such as the timing and amount of future restructuring actions and acquisition-related charges as well as gains or losses from sales of real estate and businesses, the early retirement of debt and the outcome of legal proceedings. The timing and amount of these items are uncertain and could be material to Thermo Fisher’s results computed in accordance with GAAP.

Conference Call

Thermo Fisher Scientific will hold its earnings conference call today, January 30, 2019, at 8:30 a.m. Eastern time. To listen, dial 877-273-7122 within the U.S. or 647-689-5496 outside the U.S. You may also listen to the call live on our website, www.thermofisher.com, by clicking on "Investors." You will find this press release, including the accompanying reconciliation of non-GAAP financial measures and related information, in that section of our website under "Financial Results." An audio archive of the call will be available under "Webcasts and Presentations" through Friday, February 8, 2019.

Can-Fite’s Drugs’ Potential Ability to Treat Cytokine Release Syndrome in Cancer Immunotherapy Published in Scientific Journal

On January 30, 2019 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE:CFBI), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address cancer, liver and inflammatory diseases, reported that Drug Design, Development and Therapy has published an article titled, "Targeting the A3 Adenosine Receptor to Treat Cytokine Release Syndrome in Cancer Immunotherapy (Press release, Can-Fite BioPharma, JAN 30, 2019, View Source [SID1234532965])." The article presents data from numerous studies that show adenosine’s role in inhibiting inflammatory cytokine production. Can-Fite’s Piclidenoson, a Phase III drug candidate, and Namodenson, a Phase II drug candidate, both target the A3 adenosine receptor (A3AR), which the Company believes may treat cytokine release syndrome (CRS) while also promoting an anti-cancer effect.

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CRS is a potentially life threatening side effect of cancer immunotherapies including CAR-T. The market for CAR-T drugs is estimated to reach approximately $5.4 Billion in 2024 according to Evaluate Pharma.

"While CAR-T and other cancer immunotherapies are saving lives, as their use increases, there is growing concern about the drugs’ life threatening side effects including the high incidence of CRS. With the publication of this article in Drug Design, Development and Therapy, we are advancing the scientific community towards delivering immunotherapies that offer a high degree of efficacy with a greater degree of safety for the patient. Our platform technology, through Namodenoson, has already displayed its anti-cancer effects in humans, and therefore it is a candidate to not only protect patients from CRS, but to also boost the body’s fight against cancer," stated Dr. Pnina Fishman, Can-Fite’s CEO. "We look forward to implementing our development strategy for our drugs in the treatment of CRS."

Can Fite’s platform technology selectively targets A3AR, which plays a central role in mediating the mechanism of inflammation by reducing elevated levels of pro-inflammatory cytokines such as IL-6, IL-1β, NF-Kβ, TNF-α, and more.

Eureka Therapeutics Announces US FDA Clearance of IND Application for Phase 1/2 Trial of ET140202 Artemis T-Cell Therapy, for the Treatment of Liver Cancer

On January 30, 2019 Eureka Therapeutics, Inc., a clinical stage biotechnology company developing antibody-TCR (AbTCR) T-cell therapies, reported that the U.S. Food and Drug Administration (FDA) has cleared its investigational new drug (IND) application for ET140202 ARTEMIS T-cell therapy in AFP-positive patients with advanced hepatocellular carcinoma (HCC), the most common type of liver cancer (Press release, Eureka Therapeutics, JAN 30, 2019, View Source [SID1234532966]).

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The Company plans to initiate its Phase 1/2 US multicenter clinical trial in the first half of 2019. The Phase 1 dose escalation portion of the trial will assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of ET140202. A dose expansion phase is planned to follow the selection of a recommended Phase 2 dose.

As previously reported in September 2018, Eureka presented data from a first-in-human study of ET140202 in China. The findings from the First Affiliated Hospital of Xi’An Jiaotong University demonstrated a favorable safety profile of ET140202 T-cell therapy in six patients with no observed cytokine release syndrome (CRS) or drug-related neurotoxicity. In addition, one patient in the i.v. arm of the study had a complete response. Overall, tumor regression was observed in three out of six patients.

"This is an exciting time for Eureka as we prepare to initiate our US clinical trial in patients with hepatocellular carcinoma," said Cheng Liu, Ph.D., President and Chief Executive Officer of Eureka Therapeutics. "HCC is an area of significant unmet medical need and patient options are currently limited. We intend to advance ET140202 as rapidly as possible in the US and to build upon the experience from our promising proof-of-concept study in China."

ABOUT LIVER CANCER

A highly unmet medical need, liver cancer is the second most common cause of cancer-related deaths, with roughly 600,000 patient deaths every year worldwide. Hepatocellular carcinoma (HCC) is the predominant type of liver cancer that occurs in approximately 31,500 newly diagnosed patients per year in the United States. General 5-year survival rate of liver and intrahepatic bile duct cancer in the United States is only 18%.

ABOUT ET140202

ET140202 utilizes Eureka’s proprietary ARTEMIS T-cell receptor platform engineered with a proprietary human TCR-mimic (TCRm) antibody to target an AFP-peptide/HLA-A2 complex on HCC cancer cells. Using its proprietary E-ALPHA antibody discovery platform, Eureka developed a TCRm antibody to selectively bind an AFP peptide displayed on the cell surface by the HLA-A2 major histocompatibility complex (MHC).

Newly Published Pre-Clinical Data Show Intratumoral Injections of Messenger RNA Encoding Three Immune Modulators Stimulate Durable Anti-Cancer Responses in Treated and Distal Tumors

On January 30, 2019 Moderna, Inc., (Nasdaq: MRNA) a clinical stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients, reported the publication of pre-clinical data that shows the therapeutic potential of mRNA-2752, an investigational mRNA immuno-oncology therapy that encodes a novel combination of three immunomodulators designed to activate the immune system to recognize and eradicate tumors that are resistant to checkpoint inhibitors (Press release, Moderna Therapeutics, JAN 30, 2019, View Source [SID1234532967]).

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The study, published in the scientific journal Science Translational Medicine, found that the local delivery of mRNA encoding the secreted cytokines IL23 and IL36γ and the membrane-bound T-cell co-stimulator OX40L, induced a broad immune response promoting tumor regression in both injected lesions and distant un-injected tumors in mice. When combined with checkpoint inhibitors, mRNA-2752 boosted complete response rates in immunosuppressive and in immunologically barren tumor models that are otherwise unresponsive to checkpoint inhibitors.

"These pre-clinical data are important because they show how we can utilize multiple mRNAs encoding for immune modulators in a single therapy to activate a robust, systemic immune response against cancer in immunosuppressive and in so-called ‘cold’ tumors that are resistant to checkpoint inhibitors," said Joshua Frederick, Ph.D., Moderna’s head of oncology research. "We were pleased to discover the cooperation of the components encoded by this mRNA mixture in engaging innate immune cells, innate-like lymphocytes and effector T cells, ultimately resulting in complete tumor regressions and protective immunity in our mouse models of cancer."

"Unlike conventional biologics, we believe mRNA therapies can uniquely alter the tumor microenvironment to make cancers more susceptible to checkpoint inhibitors via a paracrine effect by producing high, local therapeutic concentrations of membrane-bound and secreted immunomodulators, both of which are believed to play a critical role in the immune response against cancer," said Tal Zaks, M.D., Ph.D., chief medical officer at Moderna. "This important study highlights why we are excited to have started our Phase 1 clinical study for mRNA-2752, as we believe the combination of these immune signals has the potential to help patients for whom checkpoint inhibitors alone have been insufficient."

The study showed that in a MC38-R mouse cancer model that is considered immunosuppressive and found to be unresponsive to checkpoint inhibitor immunotherapy, a single dose of the Triplet administered intratumorally led to complete responses (defined as the absence of all detectable cancer). After multiple injections in the immunosuppressive tumor model, complete response rates increased to a majority of the treated animals. In addition, a single dose of the Triplet led to near-complete control of both injected tumors and distal untreated tumors. The addition of anti-PD-L1, anti-PD-1 or anti-CTLA-4 checkpoint inhibitors to a single dose of the Triplet improved complete response rates over either mRNA or antibody treatment alone.

Moderna has advanced mRNA-2752 into a Phase 1 study (ClinicalTrials.gov Identifier: NCT03739931) and has started dosing patients with advanced or metastatic solid tumor malignancies or lymphoma. The open label, multi-center study is evaluating the safety and tolerability of mRNA-2752 as a monotherapy or in combination with either AstraZeneca’s durvalumab (anti-PD-L1 antibody) or tremelimumab (anti-CTLA-4 antibody) and will assess anti-tumor activity, protein expression in tumors and pharmacokinetics and exploratory endpoints that include assessment of immunological response.

A link to the publication, Durable anti-cancer immunity from intratumoral administration of IL-23, IL-36γ and OX40L mRNAs (S. L. Hewitt, et. al.), can be found here.