On April 17, 2018 Celgene Corporation (NASDAQ: CELG) reported to present at three upcoming investor conferences where Celgene management will provide an overview of the Company (Press release, Celgene, APR 17, 2018, View Source [SID1234525421]). The conferences will be webcast live and will be available in the Investor Relations section of the Company’s website at www.celgene.com.

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Tuesday, May 8, 2018, Celgene will present at the Deutsche Bank 43rd Annual Health Care Conference in Boston at 12:50 pm ET
Wednesday, May 16, 2018, Celgene will present at the Bank of America Merrill Lynch Health Care Conference in Las Vegas at 1:00 pm ET
Wednesday, May 30, 2018, Celgene will present at the Sanford C. Bernstein Strategic Decisions Conference in New York City at 3:00 pm ET

On April 17, 2018 H3 Biomedicine Inc., a clinical stage biopharmaceutical company specializing in the discovery and development of next-generation cancer medicines using its data science and precision chemistry product engine, reported novel findings from a comprehensive genomic analysis of 6,235 patients across 15 hematologic malignancies (Press release, H3 Biomedicine, APR 17, 2018, View Source [SID1234525440]). The results include the first-ever observance of recurrent RNA splicing factor mutations in non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM). While splicing factor mutations have been observed in other hematologic malignancies, including myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML) and chronic lymphocytic leukemia (CLL), the presence of these mutations in NHL and MM has not been reported previously.

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Presented today at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, these new findings demonstrate the continued emergence of splicing factor mutations as a hallmark of dozens of hematologic and solid tumor cancers, their potential role in tumor formation and growth, and, thus, the opportunity to advance a new class of therapies.
At the AACR (Free AACR Whitepaper) meeting, Dominic Reynolds, Ph.D., Vice President of Chemistry at H3 Biomedicine, also gave an oral presentation discussing the discovery of H3B-8800, the Company’s first-in-class potent, selective and orally bioavailable small molecule modulator of the SF3b complex currently in Phase I clinical trials in patients with AML, CMML and MDS with splicing factor mutations.
"We continue to uncover new insights into the prevalence of splicing factor mutations across a broad spectrum of hematologic and solid tumor cancers and are leveraging this knowledge for our existing development programs and to inform the discovery of new targets and drugs," said Peter Smith, Ph.D., chief scientific officer at H3 Biomedicine. "For example, our work presented at AACR (Free AACR Whitepaper) describes mutations that are addressed by our lead splicing modulator, H3B-8800, which we’re already evaluating in AML, MDS and CMML patients in an ongoing Phase 1 clinical study. These new findings of mutations in non-Hodgkin’s lymphoma and multiple myeloma could expand the addressable patient population for H3B-8800."

Dr. Smith continued, "Beyond our own development efforts, we hope the novel insights from this research will help advance the oncology community’s understanding of the pathogenesis of multiple myeloma and non-Hodgkin’s lymphoma and stimulate new drug discovery programs to help patients whose cancer cannot be effectively treated or cured with existing therapies."

The findings presented today were the result of an ongoing collaboration between H3 Biomedicine and Foundation Medicine Inc. (NASDAQ:FMI) to help advance the discovery and development of precision medicines in oncology. H3 Biomedicine scientists and scientists from Foundation Medicine jointly uncovered the mutations through computational biology based on the genomics data from FoundationOneHeme, Foundation Medicine’s comprehensive genomic profiling (CGP) assay for hematologic malignancies and sarcomas. H3 Biomedicine is now performing additional translational research to validate the findings.
"Comprehensive genomic profiling (CGP) is a critical tool to drive the discovery and development of precision medicines in both hematologic and solid tumor cancers," said Vincent Miller, M.D., chief medical officer at Foundation Medicine. "The inherent complexity of all cancers mandates the use of an unbiased comprehensive approach in genomic profiling to speed target identification and therapeutic options. These results obtained using FoundationOneHeme and our FoundationCore database further underscore that premise. We look forward to understanding how these findings may translate to potential new therapeutic strategies for patients."

About the Findings
H3 Biomedicine and Foundation Medicine scientists surveyed somatic mutations of several splicing factors (SF3B1, SRSF2, U2AF1, ZRSR2, DDX3X, ZMYM3, PCBP1 and U2AF2) in 6,235 patients across 15 hematological malignancies. While these mutations have been observed in MDS, AML, CMML and CLL, the frequency of these mutations in other hematological malignancies was unknown. In the analysis, 405 genes were analyzed by DNA sequencing using FoundationOneHeme,

The researchers, for the first time, identified splicing factor mutations in NHL (13.8%) and MM (9%), including hotspot somatic mutations of SF3B1, U2AF1 and SRSF2, and loss of function or missense mutations in DDX3X.
NHL-Specific Highlights
Among NHL patients, diffuse large B-cell lymphoma (DLBCL) demonstrated the highest frequency of splicing factor mutations, and these patients exhibited increased tumor mutation burden.
The RNA helicase DDX3X (an enzyme implicated in several types of cancer) was the most frequently mutated in NHL.
The majority of mutations were loss of function or missense mutations, suggesting a pathological relevance of DDX3X in lymphoid malignancies

.
MM-Specific Highlights
Among MM patients, SF3B1 and SRSF2 were the two most frequently mutated genes, and patients with these mutations also exhibited increased tumor mutation burden.
Although the most common SF3B1 mutation in hematopoietic malignancies is p.K700E, the findings revealed the most frequent SF3B1 mutation in MM is p.K666.

Findings Across All 15 Hematologic Malignancies
Consistent with prior reports, the hematopoietic malignancies that demonstrated the most frequent splicing factor mutations were CMML, MDS, AML and CLL.

In addition to mutations found across the different hematopoietic malignancies in the genes SRSF2, SF3B1, U2AF1 and ZRSR2, the researchers found DDX3X to be the fifth most frequently mutated gene, followed by ZMYM3, PCBP1 and U2AF2, indicating the importance of splicing dysregulation in hematological malignancies.
For additional details, please clink here to review the abstract.
The novel discovery of splicing factor mutations in NHL and MM underscores the potential of H3’s product engine to identify previously unknown cancer drivers for the discovery and development of next-generation targeted cancer therapies. Splicing modulation is one of several research focus areas for H3.

About RNA Splicing Factor Mutations
RNA splicing is the biological process by which pre-cursor messenger RNA (pre-mRNA) is edited into a mature messenger RNA (mRNA) and, ultimately, translated into a protein. Splicing factors carry out the editing process. They are responsible for removing introns, which are a part of a pre-mRNA molecule that do not code for proteins. When RNA splicing factors are mutated, normal RNA splicing becomes aberrant, leading to gene and protein expression changes that likely play a role in tumorigenesis
.
About H3B-8800 – H3 Biomedicine’s First-in-Class Splicing Modulator
H3 Biomedicine is advancing novel cancer therapies that target core splicing factor mutations. A Phase 1 study is underway in patients with hematologic malignancies for H3B-8800, H3 Biomedicine’s first spliceosome pathway-targeting cancer therapeutic. H3B-8800 is a potent, selective and orally bioavailable small molecule modulator of wild-type and mutant SF3b complex, a splicing factor gene. The Phase 1 study is evaluating the safety and preliminary efficacy of H3B-8800 in patients with myelodysplastic syndromes, acute myeloid leukemia, and chronic myelomonocytic leukemia who carry mutations in splicing factor genes. In February 2018, H3 Biomedicine published preclinical data in Nature Medicine demonstrating that H3B-8800 modulates RNA splicing and shows preferential antitumor activity in a range of spliceosome-mutant cancer models.

On April 17, 2018 Tocagen Inc. (Nasdaq: TOCA), a clinical-stage, cancer-selective gene therapy company, reported updated durable response data from the Phase 1 study involving patients with high-grade glioma who received Toca 511 & Toca FC at the time of surgical resection will be presented at the 2018 American Academy of Neurology (AAN) Annual Meeting and 2018 American Association of Neurological Surgeons (AANS) Annual Scientific Meeting. Previously disclosed clinical data will also be reviewed at these meetings (Press release, Tocagen, APR 17, 2018, View Source;p=RssLanding&cat=news&id=2342917 [SID1234525819]).

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Additionally, preclinical data describing the level of Toca 511 transduction required for an anti-tumor response will be presented at the 14th Annual PEGS: The Essential Protein Engineering Summit.

Details of the presentation at AAN, held April 21-27 in Los Angeles, are as follows. The full presentation will be placed on Tocagen’s website following the presentation.

Presentation Type: Oral presentation (Abstract: 1173)
Title: Toca 511 & Toca FC: Evaluation of durable response rate in the post-resection setting and association with survival in patients with recurrent high grade glioma
Presenter: Timothy Cloughesy, M.D., director of the University of California, Los Angeles, Neuro-Oncology Program
Date and Time: Tuesday, April 24, 2:00 p.m. – 2:12 p.m. PT

Details of the presentation at the AANS Annual Scientific Meeting, held April 28-May 2 in New Orleans, are as follows:

Presentation Type: Oral presentation (Abstract: 615)
Title: Evaluation of durable response rate in the post-resection setting and association with survival in patients with recurrent high grade glioma who received Toca 511 and Toca FC treatment
Presenter: Bob S. Carter, M.D., Ph.D., chief of the Massachusetts General Hospital department of neurosurgery
Date and Time: Tuesday, May 1, 11:32 a.m. – 11:42 a.m. CT

Details of the presentation at PEGS, held April 30-May 4 in Boston, are as follows. The full presentation will be placed on Tocagen’s website following the presentation.

Presentation Type: Oral presentation
Title: Replicating retroviruses for manipulation of the tumor immune ecosystem: preclinical and clinical outcomes
Presenter: Douglas Jolly, Ph.D., executive vice president of research and pharmaceutical development at Tocagen
Date and Time: Tuesday, May 1, 8:30 – 9:00 a.m. ET

About Toca 511 & Toca FC

Tocagen’s lead product candidate is a two-part cancer-selective immunotherapy comprised of an investigational biologic, Toca 511, and an investigational small molecule, Toca FC. Toca 511 is a retroviral replicating vector (RRV) that selectively infects cancer cells and delivers a gene for the enzyme, cytosine deaminase (CD). Through this targeted delivery, infected cancer cells carry the CD gene and produce CD. Toca FC is an orally administered prodrug, 5-fluorocytosine (5-FC), which is converted into an anti-cancer drug, 5-fluorouracil (5-FU), when it encounters CD. 5-FU kills cancer cells and immune-suppressive myeloid cells in the tumor microenvironment resulting in anti-cancer immune activation and subsequent tumor killing.

On April 17, 2018 Rigel Pharmaceuticals, Inc. reported that the U.S. Food and Drug Administration (FDA) approved TAVALISSE (fostamatinib disodium hexahydrate) for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment (Press release, Rigel, APR 17, 2018, View Source [SID1234605501]). TAVALISSE is an oral spleen tyrosine kinase (SYK) inhibitor that targets the underlying autoimmune cause of the disease by impeding platelet destruction, providing an important new treatment option for adult patients with chronic ITP. Rigel plans to launch TAVALISSE in the United States in late May 2018.

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"Chronic ITP is challenging to treat because the heterogeneity of the disease makes it difficult to predict how an individual patient will respond to available treatments and not all patients can find a treatment that works well for them," said James Bussel, M.D., professor emeritus of pediatrics at Weill Cornell Medicine and the principal study investigator on the FIT Phase 3 program. Dr. Bussel has served as a consultant and paid member of the advisory board for Rigel Pharmaceuticals, Inc. "The FDA approval of fostamatinib arms physicians with a new treatment option, which works via a novel mechanism."

The FDA approval of TAVALISSE was supported by data from the FIT clinical program, which included two randomized placebo-controlled Phase 3 trials (Studies 047 and 048) and an open-label extension (Study 049), as well as an initial proof of concept study. The New Drug Application (NDA) included data from 163 ITP patients and was supported by a safety database of more than 4,600 subjects across other indications in which fostamatinib has been evaluated.

"People living with chronic ITP often feel they have an invisible disease — one that can not only impact quality of life, but also be life threatening," said Caroline Kruse, executive director of the Platelet Disorder Support Association, a patient advocacy organization dedicated to ITP patients. "That’s why we encourage members of our community to learn about their disease, understand treatment strategies, and seek support so that they can advocate for their best care. The availability of a new treatment option provides the ITP community with more choices."

Different Treatment Approach
TAVALISSE is designed to inhibit SYK, a key signaling component in the body’s immune process that can lead to platelet destruction in ITP patients. TAVALISSE may address an underlying autoimmune cause of ITP by impeding platelet destruction.

"We are excited to bring this new medicine to the population of adult patients with chronic ITP in need of additional therapies. I want to thank the patients, caregivers and physicians who contributed to our fostamatinib clinical program, and also the Rigel team for all of their dedication and hard work to bring the company to this historic day," said Raul Rodriguez, president and CEO of Rigel Pharmaceuticals. "This regulatory milestone, our first product approval, validates the therapeutic effect of SYK inhibition in an autoimmune disease."

Rigel will be providing product information at the ASCO (Free ASCO Whitepaper) Annual Meeting being held June 1-5, 2018 in Chicago, Booth #24160, or you can visit www.TAVALISSE.com.

About ITP
In patients with ITP, the immune system attacks and destroys the body’s own blood platelets, which play an active role in blood clotting and healing. Common symptoms of ITP include excessive bruising, bleeding and fatigue. People suffering with chronic ITP may live with an increased risk of severe bleeding events that can result in serious medical complications or even death. Current therapies for ITP include steroids, blood platelet production boosters (TPOs) and splenectomy. However, not all patients have an adequate treatment response with existing therapies. As a result, there remains a significant medical need for additional treatment options for patients with ITP.

About TAVALISSE
Indication
TAVALISSE (fostamatinib disodium hexahydrate) tablets is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.

Important Safety Information
Warnings and Precautions

Hypertension can occur with TAVALISSE treatment. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects. Monitor blood pressure every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for blood pressure control maintenance during therapy. If increased blood pressure persists, TAVALISSE interruption, reduction, or discontinuation may be required.
Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE. Monitor LFTs monthly during treatment. If ALT or AST increase to >3 x upper limit of normal, manage hepatotoxicity using TAVALISSE interruption, reduction, or discontinuation.
Diarrhea occurred in 31% of patients and severe diarrhea occurred in 1% of patients treated with TAVALISSE. Monitor patients for the development of diarrhea and manage using supportive care measures early after the onset of symptoms. If diarrhea becomes severe (≥Grade 3), interrupt, reduce dose or discontinue TAVALISSE.
Neutropenia occurred in 6% of patients treated with TAVALISSE; febrile neutropenia occurred in 1% of patients. Monitor the ANC monthly and for infection during treatment. Manage toxicity with TAVALISSE interruption, reduction, or discontinuation.
TAVALISSE can cause fetal harm when administered to pregnant women. Advise pregnant women the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Verify pregnancy status prior to initiating TAVALISSE. It is unknown if TAVALISSE or its metabolite is present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during TAVALISSE treatment and for at least 1 month after the last dose.
Drug Interactions

Concomitant use of TAVALISSE with strong CYP3A4 inhibitors increases exposure to the major active metabolite of TAVALISSE (R406), which may increase the risk of adverse reactions. Monitor for toxicities that may require a reduction in TAVALISSE dose.
It is not recommended to use TAVALISSE with strong CYP3A4 inducers, as concomitant use reduces exposure to R406.
Concomitant use of TAVALISSE may increase concentrations of some CYP3A4 substrate drugs and may require a dose reduction of the CYP3A4 substrate drug.
Concomitant use of TAVALISSE may increase concentrations of BCRP substrate drugs (eg, rosuvastatin) and P-Glycoprotein (P-gp) substrate drugs (eg, digoxin), which may require a dose reduction of the BCRP and P-gp substrate drug.
Adverse Reactions

Serious adverse drug reactions in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which occurred in 1% of TAVALISSE patients. In addition, severe adverse reactions occurred including dyspnea and hypertension (both 2%), neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope, and hypoxia (all 1%).
Common adverse reactions (≥5% and more common than placebo) from FIT-1 and FIT-2 included: diarrhea, hypertension, nausea, dizziness, ALT and AST increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia.
Please see www.TAVALISSE.com for full Prescribing Information.

To report side effects of prescription drugs to the FDA, visit www.fda.gov/medwatch or call 1-800-FDA-1088 (800-332-1088).

Trademarks for TAVALISSE are owned by or licensed by Rigel.

Conference Call and Webcast Today at 5:00PM Eastern Time
Rigel will hold a live conference call and webcast today at 5:00pm Eastern Time (2:00pm Pacific Time).

Participants can access the live conference call by dialing (855) 892-1489 (domestic) or (720) 634-2939 (international) and using the Conference ID number 5189918. The slide presentation accompanying the conference call can be accessed from Rigel’s website at www.rigel.com/webcasts. The webcast will be archived and available for replay after the call via the Rigel website.

On April 17, 2018 Johnson & Johnson (NYSE: JNJ) reported sales of $20.0 billion for the first quarter of 2018, an increase of 12.6% as compared to the first quarter of 2017 (Press release, Johnson & Johnson, APR 17, 2018, View Source [SID1234525423]).

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Operational sales results increased 8.4% and the positive impact of currency was 4.2%. Domestic sales increased 6.1%. International sales increased 19.9%, reflecting operational growth of 10.9% and a positive currency impact of 9.0%. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 4.3%, domestic sales increased 1.3% and international sales increased 7.6%.*

Net earnings and diluted earnings per share for the first quarter of 2018 were $4.4 billion and $1.60, respectively. First-quarter 2018 net earnings included after-tax intangible amortization expense of approximately $1.0 billion and a charge for after-tax special items of approximately $0.3 billion. First-quarter 2017 net earnings included after-tax intangible amortization expense of approximately $0.2 billion and a charge for after-tax special items of approximately $0.4 billion. Excluding after-tax intangible amortization expense and special items, adjusted net earnings for the current quarter were $5.6 billion and adjusted diluted earnings per share were $2.06, representing increases of 11.8% and 12.6%, respectively, as compared to the same period in 2017.* On an operational basis, adjusted diluted earnings per share also increased 5.5%.* A reconciliation of non-GAAP financial measures is included as an accompanying schedule.

"We are pleased with the strong and consistent performance delivered by our colleagues around the world, demonstrated by our sales and EPS growth in the first quarter," said Alex Gorsky, Chairman and Chief Executive Officer. "Our Pharmaceutical business continues to deliver robust growth and we are pleased with the improvement in our Consumer business. In our Medical Devices businesses, we have areas of leadership and continue to make investments and portfolio choices to improve performance."
Mr. Gorsky continued, "The U.S. tax legislation passed late last year is creating the opportunity for us to invest more than $30 billion in R&D and capital investments in the U.S. over the next four years, which is an increase of 15%."
The Company increased its sales guidance for the full-year 2018 to a range of $81.0 to $81.8 billion, reflecting expected operational growth in the range of 4.0% to 5.0%. Additionally, the Company reaffirmed its adjusted earnings guidance for full-year 2018 to a range of $8.00 to $8.20 per share, reflecting expected operational growth in the range of 6.8% to 9.6%.

Segment Sales Performance
Worldwide Consumer sales of $3.4 billion for the first quarter 2018 represented an increase of 5.3% versus the prior year, consisting of an operational increase of 1.3% and a positive impact from currency of 4.0%. Domestic sales increased 1.6%, international sales increased 8.2%, which reflected an operational increase of 1.2% and a positive currency impact of 7.0%. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 2.0%, domestic sales increased 1.6% and international sales increased 2.3%*.
Worldwide operational results, excluding the net impact of acquisitions and divestitures, were driven by beauty products primarily NEUTROGENA, AVEENO, and Dr. Ci Labo, and international analgesics in over-the-counter products, partially offset by the negative impact of domestic baby care products.
Worldwide Pharmaceutical sales of $9.8 billion for the first quarter 2018 represented an increase of 19.4% versus the prior year with an operational increase of 15.1% and a positive impact from currency of 4.3%. Domestic sales increased 9.9%; international sales increased 33.1%, which reflected an operational increase of 22.5% and a positive currency impact of 10.6%. Sales included the impact of Actelion Ltd which contributed 7.6%, to worldwide operational sales growth. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 7.5%, domestic sales increased 2.2% and international sales increased 15.3%.*

Worldwide operational results, excluding the net impact of acquisitions and divestitures, were driven by new products and the strength of core products. Strong growth in new products include DARZALEX (daratumumab), for the treatment of patients with multiple myeloma, IMBRUVICA (ibrutinib), an oral, once-daily therapy approved for use in treating certain B-cell malignancies, a type of blood or lymph node cancer and TREMFYA (guselkumab), for the treatment of adults living with moderate to severe plaque psoriasis. Additional contributors to operational sales growth included ZYTIGA (abiraterone acetate), an oral, once-daily medication for use in combination with prednisone for the treatment of metastatic, castration-resistant prostate cancer, STELARA (ustekinumab) and international SIMPONI/SIMPONI ARIA (golimumab), biologics for the treatment of a number of immune-mediated inflammatory diseases, XARELTO (rivaroxaban), an oral anticoagulant, and INVEGA SUSTENNA/XEPLION/TRINZA/TREVICTA (paliperidone palmitate), long-acting, injectable atypical antipsychotics for the treatment of schizophrenia in adults.

During the quarter, the U.S. Food and Drug Administration (FDA) approved an additional indication for ZYTIGA (abiraterone acetate), in combination with prednisone for the treatment of patients with metastatic high-risk castration-sensitive prostate cancer and ERLEADA (apalutamide) an oral androgen receptor inhibitor for the treatment of patients with non-metastatic castration-resistant prostate cancer. In addition, the Committee for Medicinal Products for Human Use issued a positive opinion recommending marketing authorization for JULUCA (rilpivirine and dolutegravir), the first, single-pill, two-drug regimen for the treatment of human immunodeficiency virus type 1 infection.

Also in the quarter, a marketing authorization application was submitted to the European Medicines Agency for apalutamide, an oral androgen receptor inhibitor for the treatment of patients with high-risk non-metastatic castration-resistant prostate cancer.

Worldwide Medical Devices sales of $6.8 billion for the first quarter 2018 represented an increase of 7.5% versus the prior year consisting of an operational increase of 3.2% and a positive currency impact of 4.3%. Domestic sales increased 2.2%; international sales increased 12.7%, which reflected an operational increase of 4.2% and a positive currency impact of 8.5%. Sales included the partial quarter impact of the recently acquired surgical vision business which contributed 3.1%, to worldwide operational sales growth. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 1.1%, domestic sales decreased 0.2% and international sales increased 2.4%.*

Worldwide operational results, excluding the net impact of acquisitions and divestitures, were driven by ACUVUE contact lenses in the Vision Care business; electrophysiology products in the Interventional Solutions business; endocutters in the Advanced Surgery business; and trauma products in the Orthopaedics business, partially offset by declines in the Diabetes Care business and spine products in the Orthopaedics business.
During the quarter, the acquisition of Orthotaxy S.A.S., a privately-held developer of software-enabled surgery technologies, including a differentiated robotic-assisted surgery was completed. In addition, the Company announced a binding offer from Platinum Equity, a private investment firm, to acquire its LifeScan business for approximately $2.1 billion, subject to customary adjustments.

Subsequent to the quarter, ACUVUE OASYS with Transitions received 510(k) clearance from the FDA and is indicated for vision correction and the attenuation of bright light.
Additionally, Johnson & Johnson plans to implement actions across its global supply chain that are intended to enable the company to focus resources and increase investments in critical capabilities, technologies and solutions necessary to manufacture and supply its product portfolio of the future, enhance agility and drive growth. The Company expects these supply chain actions will include expanding our use of strategic collaborations, and bolstering our initiatives to reduce complexity, improving cost-competitiveness, enhancing capabilities and optimizing our network. Discussions regarding specific future actions are ongoing and are subject to all relevant consultation requirements before they are finalized.

In total, the Company expects these actions to generate approximately $0.6 to $0.8 billion in annual pre-tax cost savings that will be substantially delivered by 2022. The Company expects to record pre-tax restructuring charges of approximately $1.9 to $2.3 billion, which will be treated as a special item.