ExCellThera announces clearance by FDA and Health Canada for ECT-001 in new clinical trials in United States and Canada for the treatment of leukemia

On March 25, 2019 ExCellThera Inc., a clinical stage biotechnology company delivering molecules and bioengineering solutions to expand stem and immune cells for therapeutic use, reported that its lead technology, ECT-001, will be used as part of two new clinical trials in patients with high-risk leukemia (Press release, ExCellThera, MAR 25, 2019, View Source [SID1234535179]). The announcement follows the recent clearance of the company’s Investigational New Drug (IND) application by the U.S. Food and Drug Administration (FDA) and of a clinical trial application by Health Canada, in each case for the use of ECT-001 to treat patients with high-risk leukemia and myelodysplasia. The US-based study will be conducted at the Fred Hutchinson Cancer Centre in Seattle, Washington, with the Canadian study principally taking place at the Hôpital Maisonneuve-Rosemont in Montreal, Quebec.

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Leukemia is a cancer that begins in blood stem cells and can develop very quickly. It results in the over-production of abnormal cells, which crowd out healthy blood cells and leave the patient tired, short of breath and prone to bleeding, bruising and infection. Current treatment may include chemotherapy, radiation and a hematopoietic (blood) stem cell transplant.

"Blood stem cell transplants present a life-saving option for some patients; however, they can lead to life-threatening complications," said Dr. Guy Sauvageau, CEO and founder of ExCellThera. "ECT-001 expanded blood transplants are reengineered grafts with higher quantities of stem and immune cells. Our clinical data thus far show the grafts greatly reduce the risks of post-transplant complications, including chronic graft-versus-host-disease, infection and disease relapse, resulting in better overall well-being for patients."

The two new studies are designed to be complementary and will each enrol up to 20 patients, representing geographically distinct populations. Primary endpoints include relapse free survival and incidence of transplant related mortality. Secondary endpoints include graft-versus-host disease and other infectious complications.

ExCellThera plans to initiate additional trials, including a Phase III pivotal trial in the United States and Canada, in the coming months. In December 2018, ECT-001 received FDA orphan drug designation for the prevention of graft-versus-host disease.

About ECT-001
The ECT-001 technology is a combination of a small molecule, UM171, and an optimized culture system. The technology, capable of expanding the number of stem and immune cells exponentially in as little as seven days, is used in novel curative blood transplant therapies for patients with blood cancers, allowing more rapid engraftment, greatly reduced incidence of transplant-related mortality, low risk of chronic graft-versus-host disease and low risk of relapse, resulting in better outcomes for patients.

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.

Oasmia Pharmaceutical AB receives positive opinion from the European Medicines Agency to add efficacy data to the approved Apealea® product information

On March 25, 2019 Oasmia Pharmaceutical AB (NASDAQ: OASM) reported that the European Medicines Agency (EMA) has adopted a positive opinion recommending approval of a type II variation application to add efficacy data to the Apealea product information (Press release, Oasmia, MAR 25, 2019, View Source [SID1234556567]).

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The marketing authorisation approval for Apealea in the EEA was based on the phase III pivotal study OAS‑07OVA. The study was conducted on 789 randomized patients with relapse of ovarian cancer disease that were treated with paclitaxel in combination with carboplatin. The results of the subpopulation analysis of the patients corresponding to the approved indication, i.e patients experiencing their first relapse, were based on 301 patients (Apealea arm) and 298 patients (Comparator arm).

The positive opinion of the application allows the product information to present all available efficacy data for Apealea for the approved indication in addition to the data describing the entire population. This change may be implemented after completion of the review process of the translation into all EU languages (and Norwegian and Icelandic) by the end of April 2019.

– This provides complete transparency to the physicians, as well as patients, regarding differences in efficacy between Apealea and solvent-based paclitaxel, says Mikael Asp, CEO

Information on subgroup analysis by relapse:

Subgroup analyses were conducted to investigate efficacy by relapse (first and second) in the per protocol (PP) and the intention-to-treat (ITT) populations. Progression free survival (PFS) and overall survival (OS) results in the PP population are presented in the tables below. In the intention-to-treat population, the hazard ratios (HR) for PFS in the subgroups of patients with first relapse and second relapse were 0.80 (95% confidence interval (CI): 0.66;0.97) and 1.04 (95% CI: 0.74;1.47), respectively. The hazard ratios for OS in patients with first and second relapse were 0.98 (95% CI: 0.79;1.21) and 1.18 (95% CI: 0.79;1.75), respectively. Thus, the results in the subgroup of patients with first relapse are consistent with the results in the overall population and in addition, there was an indication of PFS benefit for Apealea.

About epithelial ovarian cancer

Ovarian cancer is the seventh most common cancer in women. Approximately 239,000 women are annually diagnosed with ovarian cancer globally and 152,000 dies from the disease. Epithelial ovarian cancer is the most common form and accounts for about 90% of ovarian cancers. The disease is often diagnosed at an advanced staged since it has no symptoms at early stages. The five-year survival rate (i.e. survival of patients with ovarian cancer compared to survival in the general population at the same age) for ovarian cancer has been estimated to 38% in Europe. During 2018, approximately 68,000 women will be diagnosed with ovarian cancer in Europe and 45,000 are predicted to die from the disease. Carboplatin and paclitaxel are common chemotherapy drugs for treatment of ovarian cancer and are often used in combination.

About Apealea

Apealea is a Cremophor- and albumin-free formulation of the well-known cytostatic paclitaxel combined with Oasmia’s excipient technology XR17. Paclitaxel is one of the most widely used anticancer substances and is included in the standard treatment of a variety of cancers such as lung cancer, breast cancer and ovarian cancer. Apealea consists of a freeze-dried powder, which is dissolved in conventional solutions for infusion.

Sellas Life Sciences Group Presentation March 2019

On March 23, 2019 Sellas Life Sciences presented the corporate presentation (Presentation, Sellas Life Sciences, MAR 23, 2019, View Source [SID1234534571]).

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