Shire notes the announcement made by Takeda and confirms it has received a fourth proposal on 20 April 2018 regarding a possible offer for the Company (the "Fourth Proposal") (Press release, Shire, APR 20, 2018, View Source [SID1234525816]).

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The Fourth Proposal comprises £26 per share in new Takeda shares, to be listed in Japan and in the US through an ADR listing, and £21 per share in cash, representing a potential value of £47 per share and approximately £44 billion for the total issued and to be issued share capital of the Company. Based on Takeda’s current market capitalisation, Shire shareholders would own approximately 49 per cent. of the enlarged Takeda.

The Board of Shire is considering its position with respect to the Fourth Proposal and will issue a further announcement in due course.

This announcement is made without the consent of Takeda.

Person responsible

Stephen Williams, Deputy Company Secretary, is responsible for arranging the release of this announcement on behalf of the Company.

Publication on a website

In accordance with Rule 26.1 of the Code, a copy of this announcement will be made available, subject to certain restrictions relating to persons resident in restricted jurisdictions, on Shire’s website at www.shire.com by no later than noon (London time) on the business day following this announcement. The content of this website is not incorporated into and does not form part of this announcement.

Further information

This announcement is not intended to, and does not, constitute or form part of any offer, invitation or the solicitation of an offer to purchase, otherwise acquire, subscribe for, sell or otherwise dispose of, any securities whether pursuant to this announcement or otherwise.

The distribution of this announcement in jurisdictions outside the United Kingdom may be restricted by law and therefore persons into whose possession this announcement comes should inform themselves about, and observe, such restrictions. Any failure to comply with the restrictions may constitute a violation of the securities law of any such jurisdiction.

Citigroup Global Markets Limited, which is authorised by the Prudential Regulation Authority and regulated in the UK by the Financial Conduct Authority and the Prudential Regulation Authority in the United Kingdom, is acting for Shire and no one else in connection with the matters described in this announcement and shall not be responsible to anyone other than Shire for providing the protections afforded to clients of Citigroup Global Markets Limited, or for giving advice in connection with the matters described in this announcement or any matter referred to therein.

Goldman Sachs International, which is authorised by the Prudential Regulation Authority and regulated by the Financial Conduct Authority and the Prudential Regulation Authority in the United Kingdom, is acting for Shire and no one else in connection with the matters described in this announcement and will not be responsible to anyone other than Shire for providing the protections afforded to clients of Goldman Sachs International, or for giving advice in connection with the matters described in this announcement or any matter referred to herein.

Morgan Stanley & Co. International plc, which is authorised by the Prudential Regulation Authority and regulated by the Financial Conduct Authority and the Prudential Regulation Authority in the United Kingdom, is acting for Shire and no one else in connection with the matters described in this announcement and will not be responsible to anyone other than Shire for providing the protections afforded to clients of Morgan Stanley & Co. International plc, or for giving advice in connection with the matters described in this announcement or any matter referred to herein.

Disclosure requirements of the Code

Under Rule 8.3(a) of the Code, any person who is interested in 1% or more of any class of relevant securities of an offeree company or of any securities exchange offeror (being any offeror other than an offeror in respect of which it has been announced that its offer is, or is likely to be, solely in cash) must make an Opening Position Disclosure following the commencement of the offer period and, if later, following the announcement in which any securities exchange offeror is first identified. An Opening Position Disclosure must contain details of the person’s interests and short positions in, and rights to subscribe for, any relevant securities of each of (i) the offeree company and (ii) any securities exchange offeror(s). An Opening Position Disclosure by a person to whom Rule 8.3(a) applies must be made by no later than 3.30 pm (London time) on the 10th business day following the commencement of the offer period and, if appropriate, by no later than 3.30 pm (London time) on the 10th business day following the announcement in which any securities exchange offeror is first identified. Relevant persons who deal in the relevant securities of the offeree company or of a securities exchange offeror prior to the deadline for making an Opening Position Disclosure must instead make a Dealing Disclosure.

Under Rule 8.3(b) of the Code, any person who is, or becomes, interested in 1% or more of any class of relevant securities of the offeree company or of any securities exchange offeror must make a Dealing Disclosure if the person deals in any relevant securities of the offeree company or of any securities exchange offeror. A Dealing Disclosure must contain details of the dealing concerned and of the person’s interests and short positions in, and rights to subscribe for, any relevant securities of each of (i) the offeree company and (ii) any securities exchange offeror(s), save to the extent that these details have previously been disclosed under Rule 8. A Dealing Disclosure by a person to whom Rule 8.3(b) applies must be made by no later than 3.30 pm (London time) on the business day following the date of the relevant dealing.

If two or more persons act together pursuant to an agreement or understanding, whether formal or informal, to acquire or control an interest in relevant securities of an offeree company or a securities exchange offeror, they will be deemed to be a single person for the purpose of Rule 8.3.

Opening Position Disclosures must also be made by the offeree company and by any offeror and Dealing Disclosures must also be made by the offeree company, by any offeror and by any persons acting in concert with any of them (see Rules 8.1, 8.2 and 8.4).

Details of the offeree and offeror companies in respect of whose relevant securities Opening Position Disclosures and Dealing Disclosures must be made can be found in the Disclosure Table on the Takeover Panel’s website at www.thetakeoverpanel.org.uk, including details of the number of relevant securities in issue, when the offer period commenced and when any offeror was first identified. You should contact the Panel’s Market Surveillance Unit on +44 (0)20 7638 0129 if you are in any doubt as to whether you are required to make an Opening Position Disclosure or a Dealing Disclosure.

On April 19, 2018 Emergent BioSolutions Inc. (NYSE:EBS) reported that it will host a conference call on Thursday, May 3, 2018 at 5:00 pm (Eastern Time) to discuss the financial results for the first quarter of 2018, recent business developments, revenue guidance for the second quarter of 2018, and revenue and net income guidance for full year 2018 (Press release, Emergent BioSolutions, APR 19, 2018, View Source;p=RssLanding&cat=news&id=2343377 [SID1234525532]).

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This conference call can be accessed live by telephone or by webcast:

Live Teleconference Information:
Dial in number: (855) 766-6521
International dial in: (262) 912-6157
Conference ID: 93329114

Live Webcast Information:
Visit View Source for the live webcast feed.

A replay of the call can be accessed on Emergent’s website emergentbiosolutions.com under "Investors."

On April 19, 2018 TESARO, Inc. (NASDAQ:TSRO) reported that it will announce first-quarter 2018 financial results on Thursday, May 3, 2018, after the close of the U.S. financial markets (Press release, TESARO, APR 19, 2018, View Source [SID1234525550]). TESARO’s senior management team will host a conference call and live audio webcast at 4:15 p.m. ET on May 3, 2018 to discuss the Company’s operating results for the quarter in greater detail, as well as the status of its development programs.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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This quarterly earnings call will be available via phone and webcast. The conference call dial-in information is listed below. To access the webcast, please log on to the TESARO website at www.tesarobio.com at least 15 minutes prior to the start of the call to ensure adequate time for any software downloads that may be required.

TESARO will host a conference call and live audio webcast to discuss its first-quarter financial results.

WHEN: Thursday, May 3, 2018 at 4:15 p.m. ET
LIVE DOMESTIC & CANADA CALL-IN: (877) 853-5334
LIVE INTERNATIONAL CALL-IN: (970) 315-0307
THIS CALL WILL ALSO BE BROADCAST LIVE, LISTEN ONLY, VIA THE WEB AT: www.tesarobio.com

A replay will be available for 30 days at www.tesarobio.com.

On April 19, 2018 Personal Genome Diagnostics Inc. (PGDx) reported that its wholeexome analysis platform contributed to an important new study published in the New England Journal of Medicine (NEJM) showing promising efficacy for a leading checkpoint inhibitor in early stage lung cancer (Press release, Personal Genome Diagnostics, APR 19, 2018, View Source [SID1234525533]).1 The study also showed that patients who had higher tumor mutation burden (TMB) according to the PGDx analysis had better responses to the checkpoint inhibitor than those with lower tumor mutation loads. The study was conducted by cancer researchers from Johns Hopkins University, including PGDx co-founder Victor Velculescu, MD, PhD, and the Memorial Sloan Kettering Cancer Center (MSK). Earlier this year, PGDx announced an agreement with MSK for developing, registering and commercializing products and services that include tumor mutation burden biomarker status.

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The NEJM study reported that non-small cell lung cancer (NSCLC) patients who received the anti-PD-1 agent nivolumab before undergoing surgery for their cancer experienced fewer relapses than patients who did not.
The nivolumab-treated patients also showed signs of anti-tumor immunity stimulated by the immuno-oncology
therapy. Importantly, the study showed a direct correlation between TMB and checkpoint inhibitor response– patients with higher mutation burden scores as measured by the PGDx platform had a better response to
nivolumab—the more tumor mutations, the better the response. TMB scores were even better predictors of
response to nivolumab than measurements of PD-1 itself.

John Simmons, PhD, Director of Translational Science at PGDx, commented, "We are proud that our pioneering
work in whole exome analysis has made our platform a standard for many in the field of oncology. The analysis
generated using the PGDx exome platform (shown in Figure 3 in the NEJM study) shows a striking correlation
between tumor mutation load and response to immune checkpoint blockade. We believe that the high-quality
mutation detection approach developed at PGDx, including our proprietary VariantDxTM bioinformatics pipeline,
contributed to the strength of the results."

Dr. Simmons added, "This study also highlights the clinical relevance of TMB, even in early stage disease prior
to therapy. Whole exome analysis has been the ‘gold standard’ driving the field’s understanding of how mutation
load affects clinical response to checkpoint blockade, but it isn’t currently practical for routine clinical use. Our
ongoing initiative to translate our expertise and research applications into standardized IVD testing products for
measuring TMB and other cancer biomarkers is intended to ensure wide accessibility and use of these tools by
drug developers and physicians."

"This study is an excellent example of how the advanced scientific work of our distinguished founders gives us
the opportunity to contribute to groundbreaking cancer research while reinforcing our credibility with our industry
partners," said Doug Ward, CEO of Personal Genome Diagnostics. "Our leading VariantDx bioinformatics
analysis pipeline that informed this study and fuels our PGDx assays has allowed PGDx to be a leader in
immuno-oncology testing. We look forward to working with our growing network of partners to deliver accurate,
accessible diagnostic tests that indicate the most effective therapies for patients–an essential part of the
genomic revolution that is transforming cancer treatment."

PGDx has expertise in cancer genome analysis ranging from sample preparation and sequencing to data
interpretation and analysis. The company uses next-generation sequencing (NGS) and its proprietary algorithms
to identify alterations in complex cancer genomics and has developed novel technologies for non-invasive
approaches to cancer diagnostics. PGDx is also developing and will commercialize a portfolio of clinically
validated, regulated tissue and liquid biopsy cancer tests, enabling worldwide access to standardized NGS
testing.
1 – Neoadjuvant PD-1 Blockade in Resectable Lung Cancer, P.M. Forde, J.E. Chaft, K.N. Smith, V. Anagnostou, T.R.
Cottrell, M.D. Hellmann, M. Zahurak, S.C. Yang, D.R. Jones, S. Broderick, R.J. Battafarano, M.J. Velez, N. Rekhtman, Z.
Olah, J. Naidoo, K.A. Marrone, F. Verde, H. Guo, J. Zhang, J.X. Caushi, H.Y. Chan, J.-W. Sidhom, R.B. Scharpf, J. White, E.
Gabrielson, H. Wang, G.L. Rosner, V. Rusch, J.D. Wolchok, T. Merghoub, J.M. Taube, V.E. Velculescu, S.L. Topalian, J.R.
Brahmer, and D.M. Pardoll, New England Journal of Medicine, April 16, 2018

On April 19, 2018 Argos Therapeutics, Inc. (Nasdaq:ARGS), an immuno-oncology company focused on the development and commercialization of individualized immunotherapies based on the Arcelis precision immunotherapy technology platform, reported interim results from its randomized, active controlled, open-label, multi-center Phase 3 ADAPT trial of Rocapuldencel-T in combination with sunitinib/standard-of-care for the treatment of newly diagnosed metastatic renal cell carcinoma. Based on these results, the Company has decided to discontinue the trial (Press release, Argos Therapeutics, APR 19, 2018, View Source [SID1234525551]).

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As previously reported, a total of 462 patients with previously untreated advanced or metastatic renal cell carcinoma were enrolled in the ADAPT trial and randomized 2:1 between combination treatment with Rocapuldencel-T and sunitinib (combination arm) vs. sunitinib monotherapy (control arm) after undergoing cytoreductive nephrectomy. The Company recently submitted a protocol amendment to the U.S. Food and Drug Administration providing for four co-primary endpoints focused on various measures of survival. Based upon review of the interim data, the Company does not believe that it would achieve these endpoints if the trial were to be continued. After consulting with the principal investigators of the trial, the Company has therefore decided to discontinue the trial and has informed the FDA of its decision.

The most recent interim analysis was conducted after 51 new events (deaths) had occurred since the time of the February 2017 interim analysis. Median overall survival for the intent-to-treat patient population, one of the four co-primary endpoints, was estimated using the Kaplan-Meier method. The estimated median overall survival for the combination arm was 28.2 months (95% Confidence Interval (CI): 23.4, 35.2) compared to 31.2 months (95% CI: 23.0, 44.5) for the control arm. The hazard ratio was 1.10 (95% CI: 0.85, 1.42). The two other co-primary endpoints that were evaluated at this time, including overall survival for the patients who remained alive at the time of the February 2017 interim analysis and overall survival for all patients for whom at least 12 months of follow-up was available, also did not demonstrate a favorable result. A fourth endpoint, five-year survival, was not evaluated because there was insufficient data at this time to perform this analysis.

Based on a review of the status of its internal programs, resources and capabilities, Argos plans to explore a wide range of strategic alternatives that may include a potential merger or sale of the Company, among other potential alternatives that could maximize both near and long-term value for our shareholders. The Company has retained Stifel, Nicolaus & Company, Incorporated to serve as its financial advisor in the process.

Argos does not have a defined timeline for the exploration of strategic alternatives and is not confirming that the process will result in any strategic alternative being announced or consummated. Argos does not intend to discuss or disclose further developments during this process unless and until its Board of Directors has approved a specific action or otherwise determined that further disclosure is appropriate.

Argos also today reported that it does not expect to regain compliance with The Nasdaq Capital Market continued listing requirements by the April 24, 2018 deadline. As a result, Argos expects that its common stock will be delisted from The Nasdaq Capital Market and that trading in the Company’s common stock on The Nasdaq Capital Market will be suspended effective at the open of business on April 23, 2018. The Company has filed an application to transfer trading and quotation of its common stock to the OTCQB Venture Market, operated by OTC Markets Group Inc., under its current trading symbol "ARGS," effective as of April 23, 2018. Quotation and trading information for the common stock will be available on www.otcmarkets.com.