Statement re Proposal from Takeda Pharmaceutical Company Limited (“Takeda”)

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.

Bellicum Pharmaceuticals Announces Closing of Public Offering

On April 20, 2018 Bellicum Pharmaceuticals, Inc. (NASDAQ:BLCM) a clinical stage biopharmaceutical company focused on discovering and developing cellular immunotherapies for cancers and orphan inherited blood disorders, reported the closing of its previously announced underwritten public offering of 9,200,000 shares of its common stock, including 1,200,000 shares sold pursuant to the underwriters’ full exercise of their option to purchase additional shares, at a public offering price of $7.50 per share (Press release, Bellicum Pharmaceuticals, APR 20, 2018, View Source [SID1234525576]). The aggregate offering size was $69.0 million, before deducting the underwriting discounts and commissions and other offering expenses.

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Citigroup and Jefferies acted as lead book-running managers for the offering. Guggenheim Securities, Ladenburg Thalmann and Raymond James acted as co-managers.

TGI (Targeted Granzyme B Immunotherapy) Poster Presented at the 2018 AACR Annual Meeting

On April 20, 2018 Dr. Michael Rosenblum and his team at MD Anderson Cancer Center, Houston, TX, reported that presented updated data on TGI (Targeted Granzyme B immunotherapy) at the 2018 American Association of Cancer Research Annual Meeting (AACR) (Free AACR Whitepaper) (Press release, Mirata BioPharma, APR 20, 2018, View Source [SID1234525564]). The research was supported by Mirata Biopharma LLC and conducted by the Clayton Foundation for Research ("Clayton Foundation").

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Dr. Rosenblum’s team developed a fusion protein, GrB-Fc-IT4 (MRT-101), that contains a humanized scFv binding domain targeting the cell surface receptor Fn14, an antigen highly expressed in a variety of solid tumors, and containing the human serine protease granzyme B (GrB) as the cytotoxic payload. The construct includes the IgG hinge Fc domain linker for efficient dimerization and an overall high molecular weight, thereby designed to provide a prolonged serum half-life (~40 h in mice). This unique format mimics human immune effector cell function and induces target cell death through the activation of a variety of well described pro-apoptotic cascade signals.

The poster, entitled "Molecular mechanistic and in vivo efficacy studies of Fn14-targeted fusion constructs containing human granzyme B," demonstrated that Western blot studies on human TNBC cells (MDA-MD-231) have shown that intact MRT-101 is translocated into the cytosol in less than 1 hour after exposure and is detectable in the cytosol for at least 8 hours. The free GrB component is also detected by the Western blot 4 hours after treatment and persists for up to 8 hours. Both of these agents trigger apoptotic cascades through activation of various caspases and induction of mitochondrial damage. Studies demonstrating cytochrome C release and mitochondrial depolarization are ongoing and will be reported. Incubation with the lysosomotropic agent chloroquine did not alter the IC50 of MRT-101, suggesting that the fusion protein is not appreciably held in the endosomal compartment.

In vivo studies have shown that MRT-101 is well tolerated in BALB/c mice after intravenous administration of 5 doses at 20 mg/kg/dose. This dose level showed no evidence of toxicity in any of the major organs such as liver and kidneys. In vivo efficacy studies conducted on NSGNOD scid mice demonstrated significant tumor growth inhibition of established orthotopic breast tumors (MDA-MB-231), with no tumor growth for up to 30 days after implantation. Treatment of nude mice bearing lung PDX tumors showed a 60% tumor growth inhibition when compared to the vehicle control group. These results, in combination with previous in vitro and in vivo studies, demonstrate that the completely human MRT-101 construct is a selective, highly potent, non-toxic and effective antigen-driven drug with significant potential for the treatment of Fn14 positive tumors that acts through a new and unique mechanism of action.

Full poster from the AACR (Free AACR Whitepaper) can be accessed via Mirata Biopharma website: View Source

Varian Calypso Anchored Beacon Transponder for Lung Receives FDA 510k Clearance

On April 20, 2018 Varian (NYSE: VAR) reported it has received FDA 510(k) clearance for its Calypso Anchored Beacon transponder. Used with a Varian TrueBeam, Edge and Clinac C-series medical linear accelerators, the Calypso system and Anchored Beacon transponder detects even slight movements of a tumor and helps clinicians deliver lung stereotactic body radiotherapy (SBRT) more precisely (Press release, Varian Medical Systems, APR 20, 2018, View Source [SID1234525563]).

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The Calypso system works by implanting the Anchored Beacon transponders in small airways within or near the tumor target. The Anchored Beacon transponders feature five small "legs" that provide stable fixation to prevent the transponder from moving. The transponders emit non-ionizing electromagnetic signals that are tracked in real-time and used to keep a treatment beam on target.

The Calypso System is the only device on the market that delivers real-time, continuous (25 Hz update rate), 3D tumor position information, improving confidence that the prescribed dose has been delivered to the tumor.

"The 510(k) clearance of the Anchored Beacon transponder expands the application of the Calypso system platform," said Ed Vertatschitsch, vice president, Global Portfolio Solutions, Varian. "Using the Calypso system and Anchored Beacon transponder, clinicians can deliver dose to lung tumors with increased confidence and accuracy."

For more information on the Calypso system, visit www.varian.com/calypso.

ImmunoGen Announces Conference Call to Discuss Its First Quarter 2018 Operating Results

On April 20, 2018 ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported that the Company will host a conference call at 8:00 a.m. ET on Friday, May 4, 2018 to discuss its first quarter operating results (Press release, ImmunoGen, APR 20, 2018, View Source [SID1234525561]). Management also will provide a brief update on the business.

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Conference Call Information
To access the live call by phone, dial 719-325-4799; the conference ID is 2070974. The call may also be accessed through the Investors section of the Company’s website, www.immunogen.com. Following the webcast, a replay of the call will be available at the same location through May 18, 2018