Mavupharma Selects First Immuno-Oncology Clinical Candidate MAVU-104, an Oral STING Pathway Enhancer

On January 3, 2019 Mavupharma (Mavu) reported that it has selected its first immuno-oncology clinical development candidate, MAVU-104, a novel innate immune modulator (Press release, Mavupharma, JAN 3, 2019, View Source [SID1234537639]).

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MAVU-104 is a first-in-class, orally active, small molecule inhibitor of ENPP1, a phosphodiesterase that negatively regulates the STING (Stimulator of Interferon Genes) pathway. STING signaling plays a crucial role in the generation of an immune response directed at the tumor, and enhancing STING signaling has been shown to induce cures in multiple preclinical cancer models. Inhibiting ENPP1 activity with MAVU-104 allows for highly-controlled enhancement of STING signaling in all tumors and lymph nodes without any injections.

"With our approach, which focuses on blocking a key negative regulator of the STING pathway, as opposed to directly stimulating STING itself, the degree and duration of innate immune activation are tunable, which avoids both overstimulation of the pathway and high levels of cytokine release," stated Mike Gallatin, Ph.D., Mavu’s president and co-founder. "Having selected our first immuno-oncology drug candidate, we are now focused on the path to IND for MAVU-104, which we expect to file in the second half of 2019."

Mavu’s approach may have significant advantages over other developmental therapies that stimulate the STING pathway. Published studies on the direct STING agonists in clinical development show that these therapies are administered via direct injection into the tumor(s) and may induce release of pro-inflammatory cytokines into systemic circulation, which has been associated with side effects.

Previously, Mavu presented data at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2018 meeting showing that ENPP1 inhibition leads to tumor shrinkage and can be combined with other immunotherapies to induce long-term cures and durable immunologic memory in mouse models of cancer.

Avalon GloboCare Establishes Joint Venture with Arbele Limited to Co-develop Next-Generation Multi-Targeted CAR-T Cellular Immunotherapy

On January 3, 2019 Avalon GloboCare Corp. (NASDAQ: AVCO), a leading global developer of cell-based technologies, reported that the Company and its wholly owned subsidiary, Avactis Biosciences, have entered into a joint venture and exclusive license agreement with Arbele Limited to co-develop next generation, transposon-based Chimeric Antigen Receptor (CAR)-T and CAR-Natural Killer (NK) cellular therapies (Press release, Avalon, JAN 3, 2019, View Source [SID1234609548]). These unique CAR vector constructs are non-virally engineered, possessing multiple therapeutic targets as well as unique "safety-switch" mechanisms. Based on Avalon’s extensive hospital network for cellular therapy, together with the Company’s established GMP bio-production facility in China (Epicon Biotech, Nanjing), this joint venture allows Avalon to accelerate the clinical development of more efficacious and safer CAR-T/CAR-NK therapies, such as those developed by Arbele.

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"We are very excited to establish this joint venture with Arbele Limited to accelerate our clinical programs in cellular therapy," stated David Jin, M.D., Ph.D., CEO and President of Avalon GloboCare Corp. "Arbele’s strong proprietary technology platform in designing and production of non-viral, transposon-engineered, multi-targeted CAR will allow us to generate next-generation, better and safer CAR-T and CAR-NK cellular therapeutics. This joint venture will strengthen our core technological capabilities, enrich our intellectual properties, as well as further establish our leadership in the field of cellular immunotherapy," added Dr. Jin.

Bristol-Myers Squibb Provides 2019 EPS Guidance

On January 3, 2019 Bristol-Myers Squibb (NYSE:BMY) reported EPS guidance for full-year 2019 (Press release, Bristol-Myers Squibb, JAN 3, 2019, View Source [SID1234532386]).

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Bristol-Myers Squibb is providing its 2019 GAAP EPS guidance range at $3.75 to $3.85 and non-GAAP EPS guidance range at $4.10 to $4.20. Key 2019 GAAP and non-GAAP guidance assumptions include the combined dilution of $0.09 from the UPSA divestiture and U.S. Pension liabilities transactions.

The EPS guidance for 2019 excludes the impact of the Celgene acquisition or any potential future strategic acquisitions and divestitures, and any specified items that have not yet been identified and quantified. The non-GAAP 2019 EPS guidance also excludes other specified items as discussed under "Use of Non-GAAP Financial Information."

Bristol-Myers Squibb will provide full line-item guidance for when the company reports its results for the fourth quarter 2018 on January 24, 2019.

Bristol-Myers Squibb is providing its 2019 GAAP EPS guidance range at $3.75 to $3.85 and non-GAAP EPS guidance range at $4.10 to $4.20. Key 2019 GAAP and non-GAAP guidance assumptions include the combined dilution of $0.09 from the UPSA divestiture and U.S. Pension liabilities transactions.

The EPS guidance for 2019 excludes the impact of the Celgene acquisition or any potential future strategic acquisitions and divestitures, and any specified items that have not yet been identified and quantified. The non-GAAP 2019 EPS guidance also excludes other specified items as discussed under "Use of Non-GAAP Financial Information."

Bristol-Myers Squibb will provide full line-item guidance for when the company reports its results for the fourth quarter 2018 on January 24, 2019.

Bristol-Myers Squibb to Acquire Celgene to Create a Premier Innovative Biopharma Company

On January 3, 2019 Bristol-Myers Squibb Company (NYSE:BMY) and Celgene Corporation (NASDAQ:CELG) reported that they have entered into a definitive merger agreement under which Bristol-Myers Squibb will acquire Celgene in a cash and stock transaction with an equity value of approximately $74 billion (Press release, Bristol-Myers Squibb, JAN 3, 2019, View Source;Innovative-Biopharma-Company/default.aspx [SID1234532404]). Under the terms of the agreement, Celgene shareholders will receive 1.0 Bristol-Myers Squibb share and $50.00 in cash for each share of Celgene. Celgene shareholders will also receive one tradeable Contingent Value Right (CVR) for each share of Celgene, which will entitle the holder to receive a payment for the achievement of future regulatory milestones. The Boards of Directors of both companies have approved the combination.

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The transaction will create a leading focused specialty biopharma company well positioned to address the needs of patients with cancer, inflammatory and immunologic disease and cardiovascular disease through high-value innovative medicines and leading scientific capabilities. With complementary areas of focus, the combined company will operate with global reach and scale, maintaining the speed and agility that is core to each company’s strategic approach.

Based on the closing price of Bristol-Myers Squibb stock of $52.43 on January 2, 2019, the cash and stock consideration to be received by Celgene shareholders at closing is valued at $102.43 per Celgene share and one CVR (as described below). When completed, Bristol-Myers Squibb shareholders are expected to own approximately 69 percent of the company, and Celgene shareholders are expected to own approximately 31 percent.

"Together with Celgene, we are creating an innovative biopharma leader, with leading franchises and a deep and broad pipeline that will drive sustainable growth and deliver new options for patients across a range of serious diseases," said Giovanni Caforio, M.D., Chairman and Chief Executive Officer of Bristol-Myers Squibb. "As a combined entity, we will enhance our leadership positions across our portfolio, including in cancer and immunology and inflammation. We will also benefit from an expanded early- and late-stage pipeline that includes six expected near-term product launches. Together, our pipeline holds significant promise for patients, allowing us to accelerate new options through a broader range of cutting-edge technologies and discovery platforms."

Dr. Caforio continued, "We are impressed by what Celgene has accomplished for patients, and we look forward to welcoming Celgene employees to Bristol-Myers Squibb. Our new company will continue the strong patient focus that is core to both companies’ missions, creating a shared organization with a goal of discovering, developing and delivering innovative medicines for patients with serious diseases. We are confident we will drive value for shareholders and create opportunities for employees."

"For more than 30 years, Celgene’s commitment to leading innovation has allowed us to deliver life-changing treatments to patients in areas of high unmet need. Combining with Bristol-Myers Squibb, we are delivering immediate and substantial value to Celgene shareholders and providing them meaningful participation in the long-term growth opportunities created by the combined company," said Mark Alles, Chairman and Chief Executive Officer of Celgene. "Our employees should be incredibly proud of what we have accomplished together and excited for the opportunities ahead of us as we join with Bristol-Myers Squibb, where we can further advance our mission for patients. We look forward to working with the Bristol-Myers Squibb team as we bring our two companies together."

Compelling Strategic Benefits

Leading franchises with complementary product portfolios provide enhanced scale and balance. The combination creates:
Leading oncology franchises in both solid tumors and hematologic malignancies led by Opdivo and Yervoy as well as Revlimid and Pomalyst;
A top five immunology and inflammation franchise led by Orencia and Otezla; and
The #1 cardiovascular franchise led by Eliquis.
The combined company will have nine products with more than $1 billion in annual sales and significant potential for growth in the core disease areas of oncology, immunology and inflammation and cardiovascular disease.

Near-term launch opportunities representing greater than $15 billion in revenue potential. The combined company will have six expected near-term product launches:
Two in immunology and inflammation, TYK2 and ozanimod; and
Four in hematology, luspatercept, liso-cel (JCAR017), bb2121 and fedratinib.
These launches leverage the combined commercial capabilities of the two companies and will broaden and enhance Bristol-Myers Squibb’s market position with innovative and differentiated products. This is in addition to a significant number of lifecycle management registrational readouts expected in Immuno-Oncology (IO).

Early-stage pipeline builds sustainable platform for growth. The combined company will have a deep and diverse early-stage pipeline across solid tumors and hematologic malignancies, immunology and inflammation, cardiovascular disease and fibrotic disease leveraging combined strengths in innovation. The early-stage pipeline includes 50 high potential assets, many with important data readouts in the near-term. With a significantly enhanced early-stage pipeline, Bristol-Myers Squibb will be well positioned for long-term growth and significant value creation.
Powerful combined discovery capabilities with world-class expertise in a broad range of modalities. Together, the Company will have expanded innovation capabilities in small molecule design, biologics/synthetic biologics, protein homeostasis, antibody engineering and cell therapy. Furthermore, strong external partnerships provide access to additional modalities.
Compelling Financial Benefits

Strong returns and significant immediate EPS accretion. The transaction’s internal rate of return is expected to be well in excess of Celgene’s and Bristol-Myers Squibb’s cost of capital. The combination is expected to be more than 40 percent accretive to Bristol-Myers Squibb’s EPS on a standalone basis in the first full year following close of the transaction.

Strong balance sheet and cash flow generation to enable significant investment in innovation. With more than $45 billion of expected free cash flow generation over the first three full years post-closing, the Company is committed to maintaining strong investment grade credit ratings while continuing its dividend policy for the benefit of Bristol-Myers Squibb and Celgene shareholders. Bristol-Myers Squibb will also have significant financial flexibility to realize the full potential of the enhanced late- and early-stage pipeline.

Meaningful cost synergies. Bristol-Myers Squibb expects to realize run-rate cost synergies of approximately $2.5 billion by 2022. Bristol-Myers Squibb is confident it will achieve efficiencies across the organization while maintaining a strong, core commitment to innovation and delivering the value of the portfolio.
Terms and Financing

Based on the closing price of Bristol-Myers Squibb stock on January 2, 2019, the cash and stock consideration to be received by Celgene shareholders is valued at $102.43 per share. The cash and stock consideration represents an approximately 51 percent premium to Celgene shareholders based on the 30-day volume weighted average closing stock price of Celgene prior to signing and an approximately 54 percent premium to Celgene shareholders based on the closing stock price of Celgene on January 2, 2019. Each share also will receive one tradeable CVR, which will entitle its holder to receive a one-time potential payment of $9.00 in cash upon FDA approval of all three of ozanimod (by December 31, 2020), liso-cel (JCAR017) (by December 31, 2020) and bb2121 (by March 31, 2021), in each case for a specified indication.

The transaction is not subject to a financing condition. The cash portion will be funded through a combination of cash on hand and debt financing. Bristol-Myers Squibb has obtained fully committed debt financing from Morgan Stanley Senior Funding, Inc. and MUFG Bank, Ltd. Following the close of the transaction, Bristol-Myers Squibb expects that substantially all of the debt of the combined company will be pari passu.

Accelerated Share Repurchase Program

Bristol-Myers Squibb expects to execute an accelerated share repurchase program of up to approximately $5 billion, subject to the closing of the transaction, market conditions and Board approval.

Corporate Governance

Following the close of the transaction, Dr. Caforio will continue to serve as Chairman of the Board and Chief Executive Officer of the company. Two members from Celgene’s Board will be added to the Board of Directors of Bristol-Myers Squibb. The combined company will continue to have a strong presence throughout New Jersey.

Approvals and Timing to Close

The transaction is subject to approval by Bristol-Myers Squibb and Celgene shareholders and the satisfaction of customary closing conditions and regulatory approvals. Bristol-Myers Squibb and Celgene expect to complete the transaction in the third quarter of 2019.

Advisors

Morgan Stanley & Co. LLC is serving as lead financial advisor to Bristol-Myers Squibb, and Evercore and Dyal Co. LLC are serving as financial advisors to Bristol-Myers Squibb. Kirkland & Ellis LLP is serving as Bristol-Myers Squibb’s legal counsel. J.P. Morgan Securities LLC is serving as lead financial advisor and Citi is acting as financial advisor to Celgene. Wachtell, Lipton, Rosen & Katz is serving as legal counsel to Celgene.

Bristol-Myers Squibb 2019 EPS Guidance

In a separate press release issued today, Bristol-Myers Squibb announced its 2019 EPS guidance for full-year 2019, which is available on the "Investor Relations" section of the Bristol-Myers Squibb website at View Source." target="_blank" title="View Source." rel="nofollow">View Source

Conference Call

Bristol-Myers Squibb and Celgene will host a conference call today, at 8:00 a.m. ET to discuss the transaction. The conference call can be accessed by dialing (800) 347-6311 (U.S. / Canada) or (786) 460-7199 (International) and giving the passcode 4935567. A replay of the call will be available from January 3, 2019 until January 17, 2019 by dialing (888) 203-1112 (U.S. / Canada) or (719) 457-0820 (International) and giving the passcode 4935567.

A live webcast of the conference call will be available on the investor relations section of each company’s website at Bristol-Myers Squibb View Source and Celgene View Source." target="_blank" title="View Source." rel="nofollow">View Source

Presentation and Infographic

Associated presentation materials and an infographic regarding the transaction will be available on the investor relations section of each company’s website at Bristol-Myers Squibb View Source and Celgene View Source as well as a joint transaction website at www.bestofbiopharma.com

Syros to Present at 37th Annual J.P. Morgan Healthcare Conference

On January 3, 2019 Syros Pharmaceuticals (NASDAQ:SYRS), a leader in the development of medicines that control the expression of genes, reported that its Chief Executive Officer, Nancy Simonian, M.D., will present a corporate overview, including 2019 objectives, at the 37th Annual J.P. Morgan Healthcare Conference. Details are as follows (Press release, Syros Pharmaceuticals, JAN 3, 2019, View Source [SID1234532420]):

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37th Annual J.P. Morgan Healthcare Conference
Date: Thursday, January 10
Time: 9:00 a.m. PST (12:00 p.m. EST)
Location: Westin St. Francis Hotel, 335 Powell St., San Francisco, CA

The presentation will be followed by a question and answer session.

Live webcasts of the presentation and question and answer session will be available on the Investors & Media section of the Syros website at www.syros.com. An archived replay of both webcasts will be available for approximately 30 days.