Bristol-Myers Squibb Board of Directors Sends Letter to Shareholders Highlighting the Compelling Strategic and Financial Rationale of the Celgene Transaction; Company Provides Additional Investor Materials

On March 25, 2019 Bristol-Myers Squibb Company’s (NYSE:BMY) Board of Directors today sent an open letter to the Company’s shareholders regarding the previously reported definitive merger agreement with Celgene Corporation (NASDAQ:CELG) (Press release, Bristol-Myers Squibb, MAR 25, 2019, View Source [SID1234534585]). In addition to its March 19 investor presentation, the Company today also made available on Bristol-Myers Squibb’s website at www.bestofbiopharma.com and later today will file with the Securities and Exchange Commission (SEC) an investor presentation providing an overview of Bristol-Myers Squibb’s ability to derive value from Celgene’s pipeline and a Fact Sheet providing additional detail on key benefits of the transaction.

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The full text of the letter from the Board of Directors to shareholders follows:

Dear Fellow Shareholder:

The Board of Directors of Bristol-Myers Squibb unanimously and strongly supports the proposed acquisition of Celgene. This transaction represents a unique opportunity to create a stronger Bristol-Myers Squibb and deliver significant value for all shareholders. The combined company will be stronger today, and better positioned for sustainable long-term growth. We disagree with those shareholders that have expressed concerns with some aspects of the transaction. Your Board has conducted a rigorous evaluation process, and is highly confident that this is the best strategic option for the Company at this time. We ask for your support, and recommend that you vote your shares "FOR" the proposed transaction with Celgene.

Bristol-Myers Squibb has long been one of the world’s leading global biopharmaceutical companies whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. We believe this transaction is the best option to advance that mission, and to continue to deliver innovative medicines to our patients as a means to create long-term value for our fellow shareholders.

Our strategy has involved creating some of the leading franchises in the world from both internally developed and externally acquired sources. Leveraging our strong commercialization capabilities, we have developed five products that each currently drive over a billion dollars in annual sales, including two of the 10 largest selling drugs in the pharma industry in 2018.

By successfully executing this strategy, we have delivered financial and operational outperformance, including consistent and peer-exceeding increases in revenue, earnings and margins over the last five years. Our acute focus on sustainable growth has resulted in Bristol-Myers Squibb generating 60% of 2018 sales from new products launched over the last five years. The acquisition of Celgene takes the Company to its next chapter in a way that is fully aligned with this strategic foundation.

Bristol-Myers Squibb has transformed its product portfolio more than once, by investing internally and externally with foresight focused on our long-term growth prospects. Our business development effort has been grounded in three main pillars: (1) strategic alignment with therapeutic areas we know well, (2) compelling science focused on transformational medicines and (3) financial discipline. We believe the Celgene acquisition fits very well with these three pillars, as outlined below.

Through our broad development program and best-in-industry commercial execution, Bristol-Myers Squibb has successfully built two strong growth franchises, Eliquis and Opdivo, that currently represent ~60% of our total sales and have significant opportunity for further growth. While we expect Eliquis and Opdivo to maintain their growth well into the next decade, we are conscious of the fact that in our industry science is always evolving, product development cycles are long and these products will face eventual losses of exclusivity (Eliquis in 2026 and Opdivo beginning in 2028). As stewards for our shareholders and our patients, the Board and management team understand that now is the time to ensure that we will continue to have a robust pipeline for future growth.

Accordingly, as part of our annual comprehensive strategic review process focused on sustaining long-term growth, Bristol-Myers Squibb evaluated a full range of business development opportunities. The process was overseen by a Board comprised of directors with substantial operating experience, financial acumen, scientific expertise and investor perspectives, 10 of whom are independent including five directors who have joined the Board in the past three years.

Having reviewed a full range of opportunities, from small collaborations to transformational combinations, we identified Celgene as by far the most compelling opportunity for Bristol-Myers Squibb and its shareholders, given its strategic fit in therapeutic areas we know well, attractive value, and its unique late-stage candidates and diversified but complementary Phase 1 and 2 pipeline. The timing of the transaction was also favorable both in the near-term, as we were able to secure a very favorable price, and for the long-term, as Bristol-Myers Squibb will be strengthened and diversified (focused within our chosen therapeutic areas of oncology and immunology) in an increasingly competitive environment.

In short, the Board firmly believes that the Celgene acquisition is the right transaction at the right time for our shareholders.

A POWERFUL VALUE CREATION OPPORTUNITY FOR OUR SHAREHOLDERS

As described in greater detail in the Fact Sheet regarding this transaction, our March 19 investor presentation and our presentation regarding our ability to deliver value from Celgene’s pipeline,1 the Celgene transaction will deliver compelling value to all Bristol-Myers Squibb shareholders. The transaction will deliver:

Enhanced product leadership: The combined company will be #1 in oncology, #1 in cardiovascular and top 5 in immunology and inflammation, all of which are substantial growth areas
Diversification: Nine current products each with over $1 billion in annual sales, six near-term product launch candidates, a combined total of >50 Phase 1 and Phase 2 clinical programs and more "shots on goal"
Significantly reduced concentration of Bristol-Myers Squibb’s top 3 products in 2025 (from approximately 70% of sales on a standalone basis to approximately 45% of sales on a combined basis)
A strong late-stage pipeline: This combined pipeline includes six expected near-term product launches (including five from Celgene) representing more than $15 billion in non-risk adjusted revenue potential; of the six near-term product launches, three (ozanimod, luspatercept and fedratinib) are substantially de-risked with completed Phase 3 trials and completed or near-term submissions to the FDA for approval
Bristol-Myers Squibb’s projected total sales from Celgene’s "Big 5" (luspatercept, fedratinib, liso-cel (JCAR017), bb2121 and ozanimod) in 2025 are consistent with Street forecasts
Celgene’s "Big 5" are all first-in-class or potentially best-in-class, substantially de-risked assets with potential near-term approvals and expected to be launched in the next 12-24 months; three out of the "Big 5" have completed Phase 3/pivotal trials and two have been submitted for regulatory approval
Celgene contributes an enhanced and differentiated platform in the CAR-T space, which has significant long-term potential in oncology given the unprecedented efficacy demonstrated by this modality
The Celgene pipeline combined with Bristol-Myers Squibb’s proven and leading commercialization strength will drive tremendous value opportunities for our shareholders
A robust early-stage development pipeline: The combined pipeline includes 20 compounds in oncology IO / solid tumors, 11 in oncology/hematology, 9 in cardiovascular/fibrosis and 11 in immunology & inflammation
A conservative valuation of currently marketed products: Our valuation of Celgene’s marketed products was underpinned by conservative Revlimid forecasts. Recent positive US Patent and Trademark Office rulings make us even more confident about Revlimid
Specific, actionable synergies : The Company has done extensive due diligence to determine the $2.5 billion of sustainable, long-term synergies with identifiable sources from both current Bristol-Myers Squibb and Celgene operations. These synergies are durable given the long-term sustainability of the combined companies, included the strength of Celgene’s 5 late stage assets and broad early stage pipeline
Ideal timing : Trading ratio at two-year lows and Celgene P/E near an all-time low when deal was announced
Continued financial flexibility : Continued dividend increases and accelerated share repurchase of $5 billion expected to be executed subject to the closing of the transaction, market conditions and Board approval
A compelling value proposition : Greater than 40% accretion to Bristol-Myers Squibb standalone EPS in the first year and accretive each year thereafter through 2025, approximately 10% accretive on a discounted cash flow per share basis and IRR of 11% substantially above cost of capital. The transaction also delivers long-term strategic, operational and financial value – the combined company will have sales and earnings increases every year through 2025, and the robust pipeline provides us with many more "shots on goal" in areas that are directly aligned with our therapeutic strengths while continuing to provide financial flexibility to opportunistically source innovation externally
Before embarking on this important transaction, the Board of Directors thoroughly evaluated the acquisition against other alternatives for value creation. The nature of patent cycles in our industry means that companies like ours need to constantly rejuvenate themselves to stay ahead. Bristol-Myers Squibb has done this successfully over the past decade, and now we are focused on executing a program to supplement and eventually replace Opdivo and Eliquis – and sustaining our leadership for the future.

We don’t agree with recent suggestions to aggressively cut R&D and pursue leveraged share repurchases. Given that we operate in an industry that thrives on innovation, this approach is inconsistent with the creation of both sustainable revenue growth and long-term shareholder value. Similarly, in today’s competitive and often overpriced environment for business development, we determined that pursuing a ‘string-of-pearls’ approach to pipeline development would not deliver value or pipeline opportunities that are as compelling as acquiring Celgene.

To that end, Jim Cornelius, who initiated the ‘string-of -pearls’ strategy when he was Chairman and CEO of Bristol-Myers Squibb, agrees that the transaction with Celgene is the next natural step in Bristol-Myers Squibb’s evolution:

"The Celgene transaction enables Bristol-Myers Squibb to buy the "whole necklace" rather than stringing together individual assets. This path forward is a smart move for the long term as it eliminates paying potentially high individual premiums and minimizes certain risks associated with several smaller transactions. Bristol-Myers Squibb and Celgene are a strong strategic and cultural fit and I have already voted 100% of my Bristol-Myers Squibb shares in favor of the transaction. I have the utmost confidence the Bristol-Myers Squibb management team can deliver significant value through this deal and move the pipeline forward through commercial execution."

Bristol-Myers Squibb is a strong company today with our core franchises and internal pipeline. The Celgene transaction is a unique and compelling opportunity to diversify and further strengthen the Company, both strategically and financially, now and in the future.

For these reasons, the Bristol-Myers Squibb Board unanimously and strongly believes that the Celgene acquisition is the right transaction at the right time for Bristol-Myers Squibb shareholders – and recommends that you vote your shares "FOR" the proposed transaction with Celgene by signing, dating and returning the Company’s WHITE proxy card at your earliest convenience.

Thank you for your investment and continued support of the Company.

Sincerely,

The Bristol-Myers Squibb Board of Directors

/s/ Giovanni Caforio
Giovanni Caforio, M.D.,

Chairman and CEO

/s/ Robert J. Bertolini,

Robert J. Bertolini

/s/ Alan J. Lacy,
Alan J. Lacy

/s/ Gerald L. Storch,

Gerald L. Storch

/s/ Vicki L. Sato, Ph.D.
Vicki L. Sato, Ph.D.,

Lead Independent Director

/s/ Matthew W. Emmens,

Matthew W. Emmens

/s/ Dinesh C. Paliwal,
Dinesh C. Paliwal

/s/ Karen H. Vousden, Ph.D.,
Karen H. Vousden, Ph.D.

/s/ Peter J. Arduini,
Peter J. Arduini

/s/ Michael Grobstein,

Michael Grobstein

/s/ Theodore R. Samuels,
Theodore R. Samuels

The Bristol-Myers Squibb Board unanimously recommends that Bristol-Myers Squibb shareholders vote their shares "FOR" the approval of the issuance of shares of the Company’s common stock in connection with our proposed acquisition of Celgene prior to the Special Meeting, which will be held on April 12, 2019. All Bristol-Myers Squibb shareholders of record as of the close of business on March 1, 2019 will be entitled to vote their shares.

Bristol-Myers Squibb urges shareholders to discard any blue proxy cards and disregard any related solicitation materials sent to you by Starboard Value LP, which is soliciting proxies from Bristol-Myers Squibb shareholders against approving the merger. Irrespective of whether shareholders previously submitted a blue proxy card pertaining to the proposals contained in Bristol-Myers Squibb’s definitive proxy statement, the Company urges shareholders to cast their vote on the WHITE proxy card "FOR" the proposal to approve the transaction.

Castle Biosciences Announces Presentation of 5-Year Prospective, Multicenter Clinical Outcome Study Confirming Accuracy and Impact of Uveal Melanoma Test

On March 25, 2019 Castle Biosciences, Inc., a cancer diagnostics company providing personalized genomic information to improve cancer management decisions, reported that it will present five-year outcomes from a prospective, multicenter study showing that DecisionDx-UM accurately predicts metastatic risk for patients with uveal melanoma and is used by physicians to make patient management decisions based on risk categories determined by the test (Press release, Castle Biosciences, MAR 25, 2019, View Source [SID1234534606]). The study will be presented at the International Society of Ocular Oncology (ISOO) Biennial Conference held March 22-26 in Los Angeles CA.

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The CLEAR study (Clinical Application of DecisionDx-UM Gene Expression Assay Results) was designed to track clinical management and metastatic outcomes of patients with uveal melanoma who were tested with the DecisionDx-UM gene expression profile (GEP) test as part of their diagnostic work-up.

"An accurate understanding of metastatic risk is critical to guiding surveillance planning for patients with uveal melanoma since clinicopathologic staging alone is insufficient," commented investigator Thomas M. Aaberg, Jr., M.D., Assistant Clinical Professor at Michigan State University Medical School and ocular oncologist with Retina Specialists of Michigan, who presented the study. "The results from the CLEAR study are consistent with previous publications and confirm the accuracy and clinical utility of the DecisionDx-UM test in clinical practice."

Study Highlights:

89 patients from four centers were enrolled between March 2011 and January 2017. Median follow-up time for patients without metastasis was 4.7 years.
49 patients (55%) had a low-risk Class 1 test result; 40 patients (45%) had a high-risk Class 2 test result.
All patients with Class 2 test results were managed with high intensity surveillance (imaging and/or liver function tests every 3-6 months), while 80% of Class 1 patients were managed with low intensity surveillance (imaging and/or liver function tests at a maximum of once each year) (p<0.0001).
Overall, three (6%) Class 1 patients and 22 (55%) Class 2 patients developed metastasis (p<0.0001). Median time to metastasis was 3.2 years for Class 1 and 2.5 years for Class 2.
Five-year metastasis-free survival rates were 92% for Class 1 and 42% for Class 2 (p<0.0001).
In multivariate analysis including age, ciliary body involvement, largest basal diameter and tumor thickness, the DecisionDx-UM Class 2 result was the only statistically significant predictor of metastasis (p<0.0001).
These findings are consistent with results from previously published prospective studies documenting the accuracy of DecisionDx-UM and impact on patient management.
About DecisionDx-UM

DecisionDx-UM is a GEP test that uses an individual patient’s tumor biology to predict individual risk of metastasis. DecisionDx-UM is the standard of care in the management of uveal melanoma in the majority of ocular oncology practices. Since 2009, the American Joint Committee on Cancer (AJCC; v7 and v8) has included GEP testing for the identification of Class 1 and 2 as a prognostic factor recommended for clinical care. In 2018, the National Comprehensive Cancer Network (NCCN) published guidelines on uveal melanoma that include the DecisionDx-UM test results of Class 1A, Class 1B and Class 2B as prognostic factors to guide clinical care. DecisionDx-UM is the only prognostic test for uveal melanoma that has been validated in prospective, multi-center studies. In addition, the DecisionDx-UM test result has been shown to be a superior predictor of metastasis compared to chromosome 3 status, mutational status, AJCC stage, and cell type, as demonstrated in multiple studies.

It is estimated that nearly 8 in 10 patients diagnosed with uveal melanoma in the U.S. receive the DecisionDx-UM test as part of their diagnostic workup. More information about the test and disease can be found at www.MyUvealMelanoma.com.

NantHealth to Report 2018 Fourth-Quarter Financial Results and Host Conference Call on Thursday, March 28

On March 25, 2019 NantHealth, Inc. (NASDAQ-GS: NH), a next-generation, evidence-based, personalized healthcare company, reported that it will report financial results for its 2018 fourth quarter on Thursday, March 28, 2019, after market close (Press release, NantHealth, MAR 25, 2019, View Source;p=RssLanding&cat=news&id=2392237 [SID1234534589]). NantHealth management will host a conference call that same day at 1:30 p.m. PT (4:30 p.m. ET) to review the company’s performance.

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The conference call will be available to interested parties by dialing 844-309-3709 from the U.S. or Canada, or 281-962-4864 from international locations, passcode 1059708. The call will be broadcast via the Internet at www.nanthealth.com.

Janssen seeks to expand use of DARZALEX ® ▼ (daratumumab) combined therapy for newly diagnosed multiple myeloma patients not eligible for transplant

On March 25, 2019 Janssen Pharmaceutical Companies of Johnson & Johnson reported the submission of a Type II Variant Application to the European Medicines Agency (EMA) for DARZALEX ▼ (daratumumab) in combination with lenalidomide and dexamethasone (Rd) for the treatment of newly diagnosed patients with multiple myeloma who are not eligible for autologous stem cell transplantation (GATS) (Press release, Johnson & Johnson, MAR 25, 2019, View Source [SID1234534607]).

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"Today’s submission brings us a little closer to our goal of improving treatment outcomes for people newly diagnosed with multiple myeloma," said José Antonio Burón Vidal, vice president of medical affairs, Europe, Middle East and Africa (EMEA) region, Janssen-Cilag Limited. "We are extremely grateful to the patients and researchers who have participated in the MAIA clinical trial program and look forward to working closely with regulatory authorities to gain approval for this new association."

The application is supported by data from the MAIA Phase 3 Study (MMY3008), which was presented at the 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper). 1 The study showed that at a median follow-up of 28 months, daratumumab-Rd significantly reduced the risk of disease progression or death by 44 percent in patients with newly diagnosed multiple myeloma who were not not eligible for transplant compared to treatment with Rd alone (risk ratio [HR] = 0.56, 95% confidence interval [CI]: 0.43-0.73, p <0.0001). 1Median progression-free survival with daratumumab-Rd has not yet been reached, compared to 31.9 months for patients who received Rd alone. 1 The addition of daratumumab resulted in more pronounced responses compared to Rd alone, including increased rates of complete response (CR) or better (48% vs. 25%) and very good partial response (VGPR) or better ( 79% vs. 53%). 1As part of the study, patient health, functional capacity, symptoms, psychosocial well-being and life satisfaction were assessed through measures to assess changes in quality of life related to health using the questionnaire of the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30) on the quality of life and the study EQ-5D-5L on the health profile of EuroQol. 2

The most common adverse events during treatment grade 3/4 for daratumumab-Rd (≥10 percent) included neutropenia (50%), lymphopenia (15%), pneumonia (14%), and anemia (12%). 1 Infusion-related reactions occurred in 41% of patients receiving daratumumab-Rd, of whom 3% were grade 3/4. 1 The incidence of the second primary invasive malignancy was 3% in the daratumumab-Rd group compared to 4% in the Rd group alone. 1 EISTs leading to death were 7% in the daratumumab-Rd group, compared to 6% in the Rd group. 1The safety profile of daratumumab was consistent with previous studies. 1,3,4,5,6,7

Daratumumab-Rd is being reviewed by the US Food and Drug Administration (FDA) as part of the Real-Time Oncology Review (RTOR) pilot program.

In Europe, daratumumab is indicated: 8

in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplantation
as monotherapy for the treatment of adult patients with recurrent and refractory multiple myeloma whose previous treatment included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated progression of the disease during the last treatment
in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy
#END#

About the MAIA 2 study
The randomized, open-label, multi-center Phase 3 study included 737 newly diagnosed patients with multiple myeloma eligible for high-dose chemotherapy and GATS, aged 45 to 90 years (median age 73). Patients were randomized to receive the combination of daratumumab-Rd or Rd alone in 28-day cycles. In the patients treated with daratumumab-Rd combination, patients received weekly 16 milligrams of daratumumab per kilogram (mg / kg) intravenously during cycles 1 and 2, every other week during cycles 3 to 6, and every 4 weeks from cycle 7. Patients in the daratumumab-Rd and Rd alone arm received lenalidomide 25 mg on days 1 to 21 of each 28-day cycle, and a weekly dose of 40 mg dexamethasone in each cycle. Patients from both treatment arms continued until disease progression or an unacceptable degree of toxicity.

About Daratumumab
Daratumumab is a novel genus that targets the CD38 gene, a surface protein that is highly expressed in multiple myeloma cells, regardless of the stage of the disease. 9,10 Daratumumab is thought to induce rapid tumor cell death through numerous immune-mediated mechanisms of action, including complement-dependent cytotoxicity and antibody-dependent cellular phagocytosis, as well as apoptosis in the course of time. which a series of cell steps inside the cell result in the death of the cell. 11A subset of suppressor cells derived from myeloid cells (CD38 + MDSCs), CD38 + regulatory T cells, and CD38 + B cells decreased with daratumumab treatment. 11 Daratumumab is being evaluated in a comprehensive clinical development program across a range of multiple myeloma therapies, including first-line and post-relapse therapies. 2,12,13,14,15,16,17,18 Ongoing or planned studies are being conducted to evaluate its potential in the treatment of other hematologic malignant and pre-malignant diseases in which CD38 is expressed, such as indolent myeloma . 19,20 For more information, please consultwww.clinicaltrials.gov .

For more information about daratumumab, please see the Summary of Product Characteristics at View Source .

In August 2012 , Janssen Biotech, Inc. and Genmab A / S entered into a worldwide agreement that granted Janssen an exclusive license to develop, manufacture and market daratumumab. 21

About Multiple Myeloma Multiple
myeloma (MM) is an incurable blood cancer that starts in the bone marrow and is characterized by excessive proliferation of plasma cells. 22 More than 48,200 people have been diagnosed with multiple myeloma in Europe in 2018, and more than 30,800 patients have died. 23 Nearly half of newly diagnosed patients do not achieve five-year survival, 24 and nearly 29% of multiple myeloma patients die within one year of diagnosis. 25

Although the treatment may lead to a remission, unfortunately, patients will most likely experience a relapse because there is currently no cure. 26 The refractory multiple myeloma is a disease which progresses within 60 days following the last treatment of the patient. 27,28 Recurrent cancer refers to the return of the disease after a period of initial, partial or complete remission. 29While some patients with multiple myeloma have absolutely no symptoms, the majority of them are diagnosed because of symptoms that may include bone problems, low blood counts, elevated calcium levels, kidney problems, or infections. . 30 Patients who relapse after treatment with standard therapies, including IP and immunomodulatory agents have a poor prognosis and have few treatment options available. 31

Veracyte Announces New Afirma Xpression Atlas Data that Advance Genomic Understanding of Medullary Thyroid Cancer

On March 25, 2019 Veracyte, Inc. (Nasdaq: VCYT) reported that new data from the Afirma Xpression Atlas suggest that the majority of newly diagnosed medullary thyroid cancers (MTC) are associated with variants from three genes (Press release, Veracyte, MAR 25, 2019, View Source [SID1234534592]). The findings shed new light on the genomic underpinning of this rare, but aggressive, form of thyroid cancer and were presented today at ENDO 2019, the Endocrine Society’s annual meeting, which is being held March 23-26 in New Orleans.

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"Our findings are important because they help us better understand the genomic drivers of medullary thyroid cancer," said Steven G. Waguespack, M.D., professor of internal medicine and pediatrics at University of Texas MD Anderson Cancer Center in Houston, who presented the new data in a guided poster session. "Moreover, this information, derived from a fine needle aspiration biopsy specimen, may help guide physicians in the preoperative evaluation, surgical planning and targeted therapy selection for patients diagnosed with this disease."

For the study, researchers evaluated 77 preoperative fine needle aspiration biopsies from thyroid nodules that were positive for MTC based on Afirma testing and which spanned a range of Bethesda System cytology classification categories (III-VI). All cases were subsequently evaluated with the Xpression Atlas, which uses RNA whole-transcriptome sequencing to detect 761 variants and 130 fusions in 511 genes that are associated with thyroid cancer. The scientists found that among the MTC cases, 55.8 percent harbored a RET variant, 9.1 percent included a KRAS variant, 7.8 percent contained an HRAS variant (some of which contained more than one of these gene alterations), while 2.6 percent of cases possessed fusions and 26.0 percent included no gene variants or fusions.

"As more is understood about the genomic makeup of thyroid cancer biology, physicians may be able to further refine their treatment plans for patients using ever-more-granular genomic information," said Giulia C. Kennedy, Ph.D., chief medical and scientific officer at Veracyte. "We believe that our Afirma offering – based on our whole-transcriptome sequencing platform – is well-positioned to serve the needs of physicians in the expanding era of precision medicine."