On January 22, 2018 Celgene Corporation (NASDAQ: CELG) and Juno Therapeutics, Inc. (NASDAQ: JUNO) reported the signing of a definitive merger agreement in which Celgene has agreed to acquire Juno (Press release, Juno, JAN 22, 2018, View Source [SID1234523416]). Under the terms of the merger agreement, Celgene will pay $87 per share in cash, or a total of approximately $9 billion, net of cash and marketable securities acquired and Juno shares already owned by Celgene (approximately 9.7% of outstanding shares). The transaction was approved by the boards of directors of both companies.

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Juno is a pioneer in the development of CAR (chimeric antigen receptor) T and TCR (T cell receptor) therapeutics with a broad, novel portfolio evaluating multiple targets and cancer indications. Adding to Celgene’s lymphoma program, JCAR017 (lisocabtagene maraleucel; liso-cel) represents a potentially best-in-class CD19-directed CAR T currently in a pivotal program for relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL). Regulatory approval for JCAR017 in the U.S. is expected in 2019 with potential global peak sales of approximately $3 billion.

"The acquisition of Juno builds on our shared vision to discover and develop transformative medicines for patients with incurable blood cancers," said Mark J. Alles, Celgene’s Chief Executive Officer. "Juno’s advanced cellular immunotherapy portfolio and research capabilities strengthen Celgene’s global leadership in hematology and adds new drivers for growth beyond 2020."

"The people at Juno channel their passion for science and patients towards a common goal of finding cures by creating cell therapies that help people live longer, better lives," said Hans Bishop, Juno’s President and Chief Executive Officer. "Continuing this work will take scientific prowess, manufacturing excellence and global reach. This union will provide all three."

The acquisition will also add a novel scientific platform and scalable manufacturing capabilities which will complement Celgene’s leadership in hematology and oncology. In collaboration with Juno’s team in Seattle, Celgene plans to expand its existing center of excellence for immuno-oncology translational medicine by leveraging Juno’s research and development facility in Seattle, WA as well as Juno’s manufacturing facility in Bothell, WA.

Strategic Rationale for Acquiring Juno

Upon completion of the acquisition of Juno, Celgene will be positioned to become a preeminent cellular immunotherapy company. The strategic advantages of this acquisition will include the opportunity to:

• Leverage a novel scientific platform and scalable manufacturing capabilities to position Celgene at the forefront of future advances in the science of cellular immunotherapy

• Accelerate Juno’s pipeline development to capture the full potential of cellular immunotherapy

• JCAR017, a pivotal stage asset, with an emerging favorable profile in DLBCL, is expected to add approximately $3 billion in peak sales and significantly strengthen Celgene’s lymphoma portfolio

• JCARH125 will enhance Celgene’s campaign against BCMA (B-cell maturation antigen), a key target in multiple myeloma

• Additional cellular therapy assets in proof-of-concept trials for hematologic malignancies and solid tumors will add to Celgene’s existing pipeline

• Accelerate revenue diversification with meaningful growth drivers beyond 2020

• Capture 100% of the global economics on all Juno’s cellular immunotherapy assets
Terms of the Agreement

Celgene will acquire all the outstanding shares of common stock of Juno through a tender offer for $87 per share in cash, or an aggregate of approximately $9 billion, net of cash and marketable securities acquired and Juno shares already owned by Celgene. The transaction has been approved by the boards of directors of both companies and is subject to customary closing conditions, including the tender of a number of shares of Juno common stock, that when taken together with the shares of Juno common stock already directly and indirectly owned by Celgene, represent at least a majority of outstanding shares of Juno common stock, and expiration of the applicable waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976. The transaction is anticipated to close in Q1:18.

Celgene expects to fund the transaction through a combination of existing cash and new debt. The resulting capital structure will be consistent with Celgene’s historical financial strategy and strong investment grade profile providing the financial flexibility to pursue Celgene’s strategic priorities and take actions to drive post 2020 growth.

The acquisition is expected to be dilutive to adjusted EPS (earnings per share) in 2018 by approximately $0.50 and is expected to be incrementally additive to net product sales in 2020. There is no change to the previously disclosed 2020 financial targets of total net product sales of $19 billion to $20 billion and adjusted EPS greater than $12.50.

J.P. Morgan Securities LLC is acting as financial advisor to Celgene on the transaction. Morgan Stanley & Co. LLC is acting as financial advisor to Juno. Legal counsel for Celgene is Proskauer Rose LLP and Hogan Lovells, and Juno’s legal counsel is Skadden, Arps, Slate, Meagher and Flom, LLP.

On January 22, 2018 Astellas Pharma Inc. (TSE: 4503, President and CEO: Yoshihiko Hatanaka, "Astellas") and Vical Incorporated (NASDAQ: VICL) reported that ASP0113, an investigational DNA vaccine being developed for cytomegalovirus (CMV)-seropositive hematopoietic stem cell transplant (HSCT) recipients, did not meet its primary or secondary endpoints in the Phase 3 HELIOS clinical trial (Press release, Astellas Pharma US, JAN 22, 2018, View Source [SID1234523370]). The vaccine was generally well tolerated, with injection-site reactions being the most commonly reported adverse event.

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Astellas is a pharmaceutical company dedicated to improving the health of people around the world. (PRNewsFoto/Astellas Pharma Inc.)

"We are disappointed that the results did not demonstrate a significant improvement in overall survival and reduction in CMV end-organ disease," said Bernhardt G. Zeiher, president of Development, Astellas. "We would like to thank the patients and clinicians who participated in this important trial."

The Phase 3 trial was designed to evaluate the efficacy of ASP0113 compared with placebo in CMV-seropositive recipients undergoing an allogeneic stem cell transplant. Efficacy was assessed using a primary composite endpoint of overall mortality and CMV end-organ disease through the first year following the transplant, an endpoint which was not met. Secondary endpoints of time to first protocol-defined CMV viremia and time to first use of adjudicated CMV-specific antiviral therapy also were not met.

"The Phase 3 trial outcome is disappointing," said Vijay Samant, Vical’s Chief Executive Officer. "Astellas and Vical employees, the investigators and study site personnel did an outstanding job conducting this study, but unfortunately, the vaccine was unable to provide protection against all-cause mortality in this very difficult-to-treat patient population."

The Phase 3 trial was a 1:1 randomized, double-blind, placebo-controlled study that enrolled a total of 514 CMV seropositive subjects undergoing hematopoietic stem cell transplantation. Randomization was stratified by donor-recipient relatedness and donor CMV serostatus. Subjects were followed for one year post-transplant. For more information about the ASP0113 clinical trial, please visit www.clinicaltrials.gov.

About Cytomegalovirus
CMV is a herpes virus that is estimated to infect more than half of all adults in the United States by age 50, and is even more widespread in developing countries. A healthy immune system typically protects an infected person against CMV disease, but does not prevent or clear latent infection. Individuals whose immune systems are not fully functional are at high risk of CMV reactivation, potentially leading to severe illness or death. Those at greatest risk include HCT and solid-organ transplant recipients, as well as infants born to mothers who first become infected during pregnancy.

About ASP0113
ASP0113 is an investigational vaccine candidate designed to prevent CMV disease and associated complications in CMV-seropositive HCT recipients. ASP0113 is a bivalent DNA vaccine encoding CMV phosphoprotein 65 and glycoprotein B antigens for induction of both cellular and humoral immune responses, formulated with a proprietary poloxamer-based delivery system. ASP0113 was initially developed by Vical which partnered with Astellas for further development and commercialization. ASP0113 received Orphan Drug Designation in the United States and Europe.

On January 22, 2018 Redx Pharma Plc (LON:REDX) reported that it has appointed a chief medical officer ahead of the imminent launch of phase I clinical trials of its lead drug (Press release, Redx Pharma, JAN 22, 2018, View Source [SID1234524742]).

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Dr Andrew Saunders has 25 years in the cancer field and was recruited from Lytix Biopharma, a Norwegian immuno-oncology firm, where he held the same role.

He will work with the research and development team at Redx, "fronting" the clinical development of RXC004.

This is a potentially potent small molecule drug called a porcupine inhibitor that targets Wnt pathway.

Chairman Iain Ross said he was "very pleased" to announce Saunders’ appointment.

"He brings to the company a wealth of relevant experience and expertise in the clinical development of oncology drugs," Ross explained.

"This will be invaluable as the company transforms into a clinical stage company with the anticipated commencement of the first phase I study on lead compound RXC004 in the coming weeks.

"We are very excited by the potential of RXC004 to make a major difference in cancer treatment.

"We intend to progress RXC004 in the clinic both as a monotherapy and in combination with a checkpoint inhibitor. Therefore, we envisage that Andrew’s recent experience in immuno-oncology combination trials will be particularly pertinent to the design and execution of future clinical trials with RXC004."

Porcupine inhibitors such as RXC004 are a new and potentially breakthrough method of fighting the killer disease.

They work by targeting cancer stems cells that can often lie dormant after traditional treatment and are associated with a recurrence of the illness. Kill the stem cells and you have a chance of eradicating the disease completely.

Clinical trials of the new Redx drug commence in the "coming weeks".

On January 22, 2018 Agilent Technologies Inc. (NYSE: A) reported that it will release first-quarter fiscal 2018 financial results after the stock market closes on February 14 (Press release, Agilent, JAN 22, 2018, http://www.agilent.com/about/newsroom/presrel/2018/22jan-gp17027.html [SID1234523889]). The company will host a live webcast of its investor conference call in listen-only mode.

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Date: Wednesday, February 14, 2018
Time: 1:30 p.m. (Pacific Time)
Web access: http://www.investor.agilent.com

Listeners may log on and select "Q1 2018 Agilent Technologies Inc. Earnings Conference Call" in the "News & Events — Calendar of Events" section. The webcast will remain on the company site for 90 days.

In addition, a telephone replay of the conference call will be available at approximately February 14, 2018 at 4:30 p.m. (Pacific Time) after the call and through February 21 by dialing +1 855 859-2056 (or +1 404 537 3406 from outside the United States) and entering pass code 1482568.

On January 22, 2018 The biopharmaceutical company MOLOGEN AG (ISIN DE0006637200; Frankfurt Stock Exchange Prime Standard: MGN) reported data on its lead compound, the TLR9 agonist and immune surveillance reactivator lefitolimod, at the Annual 2018 Gastrointestinal Cancers Symposium (ASCO GI) in San Francisco (18 – 20 January 2018) (Press release, Mologen, JAN 22, 2018, View Source [SID1234523467]).

Monotherapy with lefitolimod resulted in a beneficial modulation of the tumor microenvironment (TME) associated with a reduced tumor growth in a murine model of colorectal cancer. The beneficial lefitolimod-induced modulation of the TME strongly supports its potential as cancer immunotherapeutic agent. Hence, in addition to its potential in monotherapy, lefitolimod may also be an ideal partner for immuno-oncology combination approaches, i.e. with checkpoint inhibitors.

"Beneficial modulation of the TME, in other words making immunologically "cold" tumors "hot", is a crucial requirement for the response to immunotherapeutic approaches. The presented data clearly support the mode-of-action of lefitolimod in our late-stage IMPALA study with single-agent lefitolimod in colorectal cancer. In addition they provide an excellent rationale for combining lefitolimod with checkpoint inhibitors. We know that checkpoint inhibitors need help to fully unfold their enormous potential and we believe that our TLR9 agonist lefitolimod will play a major role also in this context", said Dr Matthias Baumann, CMO of MOLOGEN AG.

Beneficial lefitolimod-induced modulation of the TME

After intratumoral injection of lefitolimod an increased infiltration of T cells (CD3+ T cells, especially CD8+ T cells) into the tumor was observed. Furthermore, also an increase of activated CD8+ T cells with cytolytic ("cell destruction capability") potential was determined. In addition, the injection of lefitolimod had a positive impact regarding so-called tumor-associated macrophages – immune cells that interact with tumor cells to influence the initiation, growth and metastasis of tumors. Lefitolimod led to an increase of anti-tumor M1-type macrophages within the tumor, accompanied with a decrease of pro-tumorigenic M2-type macrophages.
Importantly, this beneficial TME modulation from an immunosuppressed ("cold") towards a more immunoreactive ("hot") stage translated into a reduction of tumor growth in the mice.

Lefitolimod as a partner for immuno-oncological combination therapies

The lefitolimod-induced pathway provides the rationale for combining lefitolimod with checkpoint inhibitors. Response rates to checkpoint inhibitor immunotherapy vary between different tumor entities and depend on the nature of the TME. "Hot" tumors with a T cell infiltrated TME show better responses. Therefore modulation of the TME is a crucial requirement for the response to immunotherapeutic approaches.
First combination data of lefitolimod with checkpoint inhibitors have been presented at the ASCO (Free ASCO Whitepaper) GI 2017. The data showed that lefitolimod can significantly improve the anti-tumor effect of checkpoint inhibitors, particularly anti-PD-1 and anti-PD-L1 antibodies, and thus prolong survival in murine tumor models.

For more information on ASCO (Free ASCO Whitepaper) GI please visit the website:
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