Evotec and Carna Biosciences Collaborate on Indigo Platform

On May 8, 2018 Evotec AG (Frankfurt Stock Exchange: EVT, TecDAX, ISIN: DE0005664809) reported a strategic collaboration with Carna Biosciences, Incorporated ("Carna"). Carna will access Evotec’s INDiGO platform to accelerate the development of its programme CB-1763, which is being developed for the treatment of blood cancer, through to the submission of an Investigational New Drug Application ("IND") with the U.S. Food and Drug Administration (Press release, Evotec, MAY 8, 2018, View Source [SID1234526179]).

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"We are excited to initiate IND-enabling studies for our next-generation non-covalent BTK inhibitor, CB-1763, in collaboration with Evotec", said Dr Masaaki Sawa, Chief Scientific Officer at Carna Biosciences. "We’ve been working with Evotec from last year and found they are a really reliable partner. We believe Evotec’s INDiGO programme and their team will help us to accelerate the development of our CB-1763 and we are confident that we will achieve our goal to reach IND-filing in the first half of 2019."

Dr Mario Polywka, Chief Operating Officer of Evotec, added: "This development of Carna’s key project directly reflects the success of our comprehensive and industry-unique INDiGO service. We are delighted to support Carna’s CB-1763 inhibitor programme, an innovative approach to blood cancer, through to the clinic. Additionally, working with Carna also highlights our increasing presence in the Japanese market."

Carna has another reversible BTK inhibitor in pre-clinical development, AS-871, a novel non-covalent BTK inhibitor targeting autoimmune diseases. AS-871 is also undergoing IND-enabling studies in collaboration with Evotec.

About Evotec’s INDiGO platform The INDiGO platform is a key value-generating component of Evotec’s broad EVT Execute business segment. INDiGO accelerates early drug candidates into the clinic by reducing time from nomination to regulatory submission in 52 weeks, and under circumstances, even less. We achieve accelerated development by tightly integrating traditional drug silos into a single project managed under one roof. The programme has been proven to reduce time and cost while achieving a quality data package for CTA/IND level regulatory filings.

Evotec’s INDiGO projects are managed by our most experienced, dedicated project managers and leading world-class drug development professionals implementing tailored development strategies designed specifically for the molecule, therapeutic area and strategic needs. The project plan is designed to integrate development areas: API Manufacture, Formulation Development, Clinical Supply, Safety Assessment, DMPK, Bioanalysis Studies and Regulatory Submission Documents Preparation.

ABOUT CARNA BIOSCIENCES, INC.

Carna Biosciences is a biopharmaceutical company focused on the discovery and development of kinase inhibitor drugs to address serious unmet medical needs. Carna has intensively focused its research efforts primarily in the areas of oncology and autoimmune/inflammation, where the company believes its extensive expertise in kinases can be most effectively leveraged. Taking advantage of Carna’s proprietary platform technologies and highly focused kinase expertise, the company continues to challenge to identify and develop innovative drugs. Carna is a publicly traded company in the JASDAQ of the Tokyo Stock Exchange with securities code 4572. For more information, please visit www.carnabio.com.

ABOUT CB-1763

CB-1763 is a highly selective, orally bioavailable, non-covalent inhibitor of Bruton’s tyrosine kinase (BTK) with a potential application in the treatment of blood cancer. Recent studies have indicated that the emergence of BTK mutations causes ibrutinib resistance. A selective and non-covalent BTK inhibitor is therefore highly demanded to overcome the emerging unmet medical need of ibrutinib resistance. CB-1763 is a next-generation non-covalent BTK inhibitor, designed to inhibit both BTK wild type and BTK C481 mutants in a highly selective and reversible manner.

MEDIA CONTACT:
CORPORATE PLANNING
CARNA BIOSCIENCES, INC.
TEL: +81-78-302-7075

Proposed Acquisition of Shire plc by Takeda

On May 8, 2018 Takeda Pharmaceutical Company Limited (TSE: 4502) ("Takeda") and Shire plc (LON: SHP) ("Shire") reported that they have reached agreement on the terms of a recommended offer pursuant to which Takeda will acquire the entire issued and to be issued ordinary share capital of Shire (Press release, Takeda, MAY 8, 2018, View Source [SID1234526178]). Under the terms of the acquisition, each Shire shareholder will be entitled to receive $30.33 in cash for each Shire share and either 0.839 new Takeda shares or 1.678 Takeda ADSs. The transaction has been approved by both companies’ boards of directors, and is expected to close in the first half of calendar year 2019. Upon the closing of the transaction, Takeda shareholders will own approximately 50 percent of the combined group.

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With leading market positions in prioritized therapeutic areas, an attractive geographic footprint, greater scale and efficiencies, and an even more productive R&D engine, the combined group will be better positioned to deliver highly-innovative medicines and transformative care providing better health and a brighter future for patients around the world.

"Since its inception, Takeda has transformed into an agile, R&D-driven global pharmaceutical company that is well-positioned to deliver innovative and transformative care to patients around the world," said Christophe Weber, president and chief executive officer of Takeda. "Shire’s highly complementary product portfolio and pipeline, as well as experienced employees, will accelerate our transformation for a stronger Takeda. Together, we will be a leader in providing targeted treatments in gastroenterology, neuroscience, oncology, rare diseases and plasma-derived therapies. We are looking forward to the benefits this combination will bring to patients worldwide, the opportunities it will bring for our employees and the returns it will deliver for our shareholders."

Susan Kilsby, chairman of Shire, said, "Over the last 30 years, Shire has become the global leader in treating rare diseases, delivering innovative products that transform patients’ lives. With this combination, Shire helps create an even stronger biopharmaceutical company, with a robust R&D pipeline and expanded global footprint. We are proud of what Shire has become and are grateful to all Shire employees for their contributions. We firmly believe that this combination recognizes the strong growth potential of our leading products and innovative pipeline and is in the best interests of our shareholders, our patients and the communities we serve."

Flemming Ornskov, chief executive officer of Shire, said, "I would like to thank the entire Shire team for all that we have accomplished over the last five years to transform Shire into a leading rare disease biotech company and a tenacious champion for patients in need. I am confident that this relentless focus will enable us to continue delivering against our priorities throughout this process. With a truly innovative portfolio and pipeline, I believe that the combination of the two companies is in the best interests of shareholders and offers an opportunity to improve the lives of even more patients globally with rare and highly specialized conditions."

Highly Compelling Strategic and Financial Rationale

Brings together complementary positions in GI and neuroscience; provides leading positions in rare diseases and plasma-derived therapies to complement strength in oncology and focused efforts in vaccines

The acquisition of Shire will accelerate Takeda’s transformation by bringing together Takeda and Shire’s complementary positions in GI and neuroscience. It will also provide the combined group with leading positions in rare diseases and plasma-derived therapies to complement strength in oncology and focused efforts in vaccines. Takeda will continue to focus on the acceleration of its oncology business, following its recent acquisition of ARIAD Pharmaceuticals. In addition, Takeda’s vaccine business will continue to address the world’s most pressing public health needs.

Creates a global, values-based, R&D-driven biopharmaceutical leader headquartered in Japan, with an attractive geographic footprint and provides the scale to drive future development

The acquisition will build on Takeda’s long Japanese heritage and values-based culture to create a global biopharmaceutical leader, driven by innovative and world-class R&D. The combined group will have an attractive geographic footprint, with significantly increased exposure in the United States (U.S.), an important and growing market. In addition, Shire’s portfolio will benefit from Takeda’s strong international presence in emerging markets and Japan. The integrated company will continue to be headquartered in Japan, expand its R&D presence in the Boston area and have major regional locations in Japan, Singapore, Switzerland and the U.S. Together, the combined group will have leading positions in two of the largest drug markets globally: the U.S. and Japan. The acquisition is expected to result in Takeda being the only pharmaceutical company listed on both the Tokyo Stock Exchange in Japan, where it will continue to have its primary listing, and the NYSE in the U.S., enabling it to access two of the world’s largest capital markets.

Creates a highly complementary, robust, modality-diverse pipeline and a strengthened R&D engine focused on breakthrough innovation

Takeda and Shire have highly complementary pipelines. Shire has strong expertise in rare diseases, an attractive modality-diverse mid- and late-stage pipeline, enriched with large-molecule programs, as well as cutting-edge technologies in gene therapy and recombinant proteins. Combining this with Takeda’s early development and research-oriented R&D program will result in a highly complementary, robust, modality-diverse pipeline and a strengthened R&D engine focused on breakthrough innovation. The combined group will build on existing partnerships, including Takeda’s more than 180 active partnerships with academia, biotechnology companies and startups, to further enrich the pipeline.

Enhances Takeda’s cash flow profile, with management committed to delivering substantial annual cost synergies and generating attractive returns for shareholders

The acquisition of Shire will provide compelling financial benefits for the combined group. It will be significantly accretive to underlying earnings per share from the first full fiscal year following completion, and will produce strong combined cash flows. The transaction is also expected to result in attractive returns for shareholders, with the return on invested capital (ROIC) expected to exceed Takeda’s cost of capital within the first full fiscal year following completion. The substantial cash flow generation expected to result from the acquisition will enable the combined group to de-lever quickly following completion. Takeda intends to maintain its investment grade credit rating, with a target net debt to EBITDA ratio of 2.0x or less in the medium term.

Takeda is confident that the acquisition will create an opportunity to recognize significant recurring cost synergies, with potential for additional revenue synergies from the combination of Shire and Takeda’s combined infrastructure, market presence and development capabilities. Takeda expects recurring pre-tax cost synergies for the combined group to reach a run-rate of at least $1.4 billion per annum by the end of the third fiscal year following completion of the acquisition.

The acquisition will accelerate Takeda’s strategic transformation toward Vision 2025, and strong combined cash flows will enable continued investment in R&D. Takeda’s well-established dividend policy will remain a key component of future shareholder returns.

Execution

Takeda’s experienced management team has a proven track record of executing complex business integrations and large-scale transformations, and is well-positioned to successfully integrate Shire and maximize the value of the combination. The integration will be supported by the companies’ highly complementary organizational structures in geographic areas, including hubs in the Boston area, Switzerland and Singapore, as well as similar therapeutic area focus and complementary approaches to R&D. Takeda is dedicated to carrying out integration efforts in a manner consistent with the company’s core values of integrity, fairness, honesty and perseverance, building on the expertise of employees of both companies.

Transaction Terms

Under the terms of the acquisition, Shire shareholders will be entitled to receive, for each Shire share, $30.33 in cash and either 0.839 new Takeda shares or 1.678 Takeda ADSs.

The acquisition terms imply an equivalent value of:

£48.17 per Shire share based on the closing price of ¥4,535 per Takeda share on May 2, 2018, and the exchange rates of £:¥ of 1:147.61 and £:$ of 1:1.3546 on May 4, 2018 (being the latest practicable date prior to this announcement); and
£49.01 per Shire share based on the closing price of ¥4,923 per Takeda Share and the exchange rates of £:¥ of 1:151.51 and £:$ of 1:1.3945 on April 23, 2018 (being the day prior to the announcement that the Shire board would, in principle, be willing to recommend the consideration).

The equivalent value of £49.01 per Shire share values the entire issued and to be issued ordinary share capital of Shire at approximately £46 billion.

Immediately following completion of the transaction, Takeda shareholders will hold approximately 50 percent of the combined group.

The transaction has been approved by the boards of both companies, and is subject to the approval of Shire and Takeda shareholders and certain customary closing conditions, including regulatory approvals.

The acquisition is expected to close in the first half of calendar year 2019. Upon completion, the new Takeda shares will be listed on the Tokyo Stock Exchange, and local Japanese stock exchanges. In addition, Takeda will apply for its ADSs (each representing 0.5 Takeda shares) to be listed on the NYSE effective on or shortly after the effective date.

Financing

Takeda has entered into a bridge facility agreement of $30.85 billion with, among others, J.P. Morgan Chase Bank N.A., Sumitomo Mitsui Banking Corporation and MUFG Bank, Ltd., part of the proceeds of which will be used to fund the cash consideration payable to Shire shareholders in connection with the acquisition. It is currently contemplated that, prior to completion, the commitments under the bridge facility agreement will be reduced or refinanced with a combination of long-term debt, hybrid capital and available cash resources.

Conference Call Webcast Information

Takeda will host a transaction conference call at 4.15pm – 5pm JST / 8.15am – 9am BST / 3.15am – 4am EST on May 8, 2018 to discuss the transaction.

Investors and analysts can dial in to the conference call using the numbers below:

Standard International Access: +44 (0) 20 3003 2666; Japan Toll Free: 006633132499; UK Toll Free: 0808 109 0700; USA Toll Free: 1 866 966 5335; Tokyo Toll Free: +81 (0) 3 5050 5366; and Passcode: 161017

A presentation for the call will be available at:

View Source

Takeda will host an additional audio webcast at 10.00 p.m. JST / 2.00 p.m. BST / 9.00 a.m. ET on May 8, 2018 with Japanese translation, to discuss the transaction. The webcast can be accessed at the following link:

View Source

Replays of the conference calls will be available within 24 hours.

For more information, the full Rule 2.7 announcement setting out full details of the offer to Shire shareholders is available at: View Source

MEDIGENE’S ACADEMIC PARTNERS PROVIDE UPDATE ON PLANNED MAGE-A1-SPECIFIC TCR CLINICAL IIT DURING CIMT

On May 8, 2018 Medigene AG (MDG1, Frankfurt, Prime Standard), reported that researchers from Max-Delbrück-Center for Molecular Medicine (MDC) and Charité, both in Berlin, Germany, will present an update on the clinical trial preparations concerning a MAGE-A1-specific T cell receptor clinical investigator-initiated trial (IIT) at the 16th Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) in Mainz, Germany, from 15 – 17 May (Press release, MediGene, MAY 8, 2018, View Source [SID1234526177]). CIMT (Free CIMT Whitepaper) is Europe’s largest meeting focused on cancer immunotherapy research and development.

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In the abstract that will be published today, the partners announce that the competent regulatory authority Paul-Ehrlich-Institute, Germany, has granted the clinical trial authorization for the planned Phase I trial and that the manufacturing license for the established GMP-compliant manufacturing process is expected to be issued in Q2 2018. More details on the trial design for the treatment of patients with relapsed or refractory multiple myeloma can be found in the abstract on the CIMT (Free CIMT Whitepaper) website: www.meeting.cimt.eu/program

The academic trial will be conducted under the responsibility of Charité and the Max-Delbrück Center. Medigene has supported both the MDC and Charité in regulatory affairs and other matters related to trial approval. Additionally, Medigene has certain rights of first negotiation for the TCR candidate utilized in this trial.

Independently, Medigene is currently conducting its own, company-sponsored phase I/II clinical trial with its proprietary TCR therapy MDG1011 in various blood cancer indications which commenced at the end of March 2018.

Medigene AG (FSE: MDG1, ISIN DE000A1X3W00, Prime Standard, TecDAX) is a publicly listed biotechnology company headquartered in Martinsried near Munich, Germany. The company is developing highly innovative immunotherapies to target various forms and stages of cancer. Medigene concentrates on the development of personalized T cell-based therapies, with associated projects currently in pre-clinical and clinical development. For more information, please visit www.medigene.com

This press release contains forward-looking statements representing the opinion of Medigene as of the date of this release. The actual results achieved by Medigene may differ significantly from the forward-looking statements made herein. Medigene is not bound to update any of these forward-looking statements. Medigene is a registered trademark of Medigene AG. This trademark may be owned or licensed in select locations only.

Aptose Exercises Early Option for CG-806 License From CrystalGenomics

On May 7, 2018 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS) and CrystalGenomics, Inc. (KOSDAQ:083790) reported that Aptose exercised its option under the 2016 Option Agreement to exclusively license CG-806, a first-in-class, non-covalent pan-inhibitor of the Bruton’s tyrosine kinase (BTK) and FMS-like tyrosine kinase 3 (FLT3) from CrystalGenomics, Inc (Press release, CrystalGenomics, MAY 7, 2018, View Source [SID1234539163]). CG-806 is being developed as a highly potent, oral small molecule for acute myeloid leukemia (AML), B-Cell malignancies and other hematologic malignancies.

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With the early exercise of the option, Aptose owns global rights to develop and commercialize CG-806 for all indications outside of Korea and China – the Licensed Territory. The exercise triggers a payment of US $2.0 million to CrystalGenomics. CrystalGenomics is eligible for regulatory and sales milestone payments, as well as royalties on product sales in the Licensed Territory.

Aptose has been conducting Investigational New Drug (IND) enabling studies with CG-806, as well as numerous preclinical studies. When tested against fresh bone marrow samples from patients with AML, CG-806 demonstrated superior potency and range of activity relative to all other FLT3 inhibitors evaluated. Likewise, CG-806 demonstrated superiority over ibrutinib when tested against samples from CLL patients. The superior potency and breadth of activity against patient-derived hematologic malignancy cells is due to the ability of CG-806 to target all wild type (WT) and all known mutant forms of FLT3 and BTK, and to suppress multiple signaling pathways that can rescue hematologic cancers from other agents. Once-daily oral dosing of CG-806 in murine xenograft models of human hematologic malignancies demonstrated tumor eradication in the absence of observable toxicity, and dose range finding studies have shown CG-806 to have a robust safety profile. Aptose expects to submit an IND in late 2018 and initiate clinical trials immediately thereafter.

"CG-806 has the potential to serve as a transformational agent for AML, chronic lymphocytic leukemia (CLL) and other hematologic malignancies," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer of Aptose. "Recent pre-clinical studies, just highlighted at the 2018 AACR (Free AACR Whitepaper) Annual Meeting, demonstrated CG-806’s superior potential to other FLT3 inhibitors on AML patient samples and superior potential to ibrutinib on CLL patient samples."

"Aptose has made the clinical development of CG-806 a priority, and we are pleased to be working with them," said Joong Myung Cho, Ph.D., Chairman and Chief Executive Officer of CrystalGenomics. "Aptose and its clinical advisors clearly recognize the potential of CG-806 as an exciting therapeutic option for patients with AML, CLL and other malignancies."

10-Q – Quarterly report [Sections 13 or 15(d)]

Cellular Biomedicine Group has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission .

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