On April 19,2018 Novartis reported the appointment of John Tsai, M.D. as Head of Global Drug Development (GDD) and Chief Medical Officer (Press release, Novartis, APR 19, 2018, View Source [SID1234525524]). Dr. Tsai will join Novartis on May 1, 2018, and will be based in Basel, Switzerland. He will report to Vas Narasimhan, M.D., CEO of Novartis and will become a member of the Executive Committee of Novartis (ECN). He succeeds Dr. Narasimhan who became CEO of Novartis on February 1, 2018. Dr. Rob Kowalski, who led GDD ad interim since February 1, 2018, will resume his responsibilities as Head of Global Regulatory Affairs for GDD.

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Dr. Tsai has been Chief Medical Officer and Senior Vice President of Global Medical at Amgen Inc., since May 2017 and oversees all clinical and medical functions across multiple sites worldwide. At Novartis, he will be responsible for advancing the company’s industry-leading pipeline of innovative medicines and biosimilars. Dr. Tsai will also lead the GDD organization’s ongoing transformation embracing the power of advanced data sciences and digital technologies to create a more agile model for drug development.

"I am delighted to welcome John to Novartis," said Dr. Narasimhan. "As we continue to reimagine drug development, his expertise across multiple therapeutic areas, including cardiovascular, oncology and neuroscience combined with his background in electrical engineering will be a source of great strength for Novartis. John has a great track record in nurturing talent across clinical development, medical affairs and development operations and shares our commitment to build an empowered and inspired organization. I also want to express my sincere gratitude to Rob Kowalski for his excellent ad interim leadership of the GDD organization."

Dr. Tsai said: "I feel honored to have the opportunity to lead the Novartis Global Drug Development organization and do my part in bringing forward the company’s strong pipeline of medicines that address some of humanity’s biggest health challenges. I am also excited to work with my colleagues at Novartis to pioneer novel paradigms for drug development with data and digital technologies at the core."

Prior to joining Amgen, Dr. Tsai spent eleven years with Bristol-Myers Squibb (BMS), where he served as Global Head of Clinical Development for marketed products and global clinical operations. He also played a leadership role in advancing the company’s late-stage pipeline across multiple therapeutic areas including cardiovascular, oncology and neuroscience. As the company’s Chief Medical Officer, Europe and prior to that, as Head of U.S. Medical and Vice President of Cardiovascular Medical, Dr.Tsai played a critical role in driving multiple transformation initiatives within the development and medical organizations. Before joining BMS, he was a cardiovascular group leader at Pfizer where he led the strategy development and execution of over 26 pivotal trials for a major cardiovascular medicine. He started his career at GE as an electrical engineer before returning to school to study medicine.

Dr. Tsai holds a medical degree from the University of Louisville School of Medicine and a Bachelor of Science in Electrical Engineering from Washington University in St. Louis. He completed his residency at Kaiser Permanente in San Francisco, California, where he then served as a physician in internal medicine, Chief Resident and as a member of the hospital’s faculty.

Disclaimer
This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as "will," "pipeline," "ongoing," "to create," "continue," "commitment," "opportunity," "excited," "to pioneer," or similar expressions, or by express or implied discussions regarding potential new products, potential new indications for existing products, or regarding potential future revenues from any such products express or regarding potential future sales or earnings of the Novartis Group. You should not place undue reliance on these statements. Such forward looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward looking statements. There can be no guarantee that any new products will be approved for sale in any market, or that any new indications will be approved for any existing products in any market, or that any approvals which are obtained will be obtained at any particular time, or that any such products will achieve any particular revenue levels. Nor can there be any guarantee Novartis will be commercially successful in the future, or achieve any particular financial results. In particular, our expectations could be affected by, among other things: regulatory actions or delays or government regulation generally; the potential that the strategic benefits, synergies or opportunities expected from the significant reorganizations of recent years may not be realized or may take longer to realize than expected; the uncertainties inherent in the research and development of new healthcare products; our ability to obtain or maintain proprietary intellectual property protection on key products; safety, quality or manufacturing issues; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures; uncertainties regarding actual or potential legal proceedings; and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

On April 19, 2018 The U.S. Food and Drug Administration (FDA) approved AstraZeneca’s Tagrisso (osimertinib) for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) in tumors with epidermal growth factor receptor (EGFR) mutations (Press release, BioSpace, APR 19, 2018, View Source [SID1234525545]).

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The mutations, exon 19 deletions or exon 21 L858R mutations, will be detected by an FDA-approved test. The decision was based on data form the Phase III FLAURA clinical trial. Results were presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Congress and published in the New England Journal of Medicine.

The FLAURA trial compared Tagrisso to current first-line EGFR tyrosine kinase inhibitors, erlotinib or gefitinib, in patients who had not received previous treatment for locally-advanced or metastatic EGFR-mutation NSCLC. It met the primary endpoint of progression-free survival, and were consistent across all pre-specified patient subgroups.

Patients receiving Tagrisso had about 18.9 months on average before the disease got worse compared to 10.2 months for patients receiving traditional treatments.

Tagrisso is a third-generation, irreversible EGFR-TKI designed to inhibit both EGFR-sensitizing and EGFR T790M-resistance mutations, with clinical activity against central nervous system cancers. It has been approved in the U.S. and Brazil for first-line EGFRm advanced NSCLC, and in more than 75 countries, including the U.S., Europe, Japan and China, for patients with EGFR T790M mutation-positive advanced NSCLC. It is also being evaluated as an adjuvant and in combination with other treatments.

It has also been approved in the U.S. for second-line treatment of patients with metastatic EGFRm NSCLC, whose disease has on or after a first-line EGFR-TKI round of therapy and who have developed the secondary T790 mutation. The drug received both Breakthrough Therapy and Priority Review designations from the FDA in 2017 for the first-line setting.

"Today’s FDA approval of Tagrisso in the first-line setting is an exciting milestone for patients and our company," said Dave Fredrickson, executive vice president, Head of the Oncology Business Unit at AstraZeneca, in a statement. "Tagrisso delivered unprecedented median progression-free survival data across all pre-specified patient subgroups, including patients with or without CNS metastases, and could prolong the lives of more patients without their tumors growing or spreading."

The drug is being evaluated in Europe and Japan as a first-line treatment, with regulatory decisions expected in the second half of this year. AstraZeneca has projected that Tagrisso could, at its peak, bring in $4 billion per year.

Lung cancer accounts for about one-fifth of all cancer deaths, more than breast, prostate and colorectal cancers combined. It is the leading cause of cancer death for both men and women. About 10 to 15 percent of patients in the U.S. and Europe and about 30 to 40 percent in Asia, have EGFRm NSCLC. They are especially sensitive to EGFR-TKI treatments, but those cancers typically develop resistance to that treatment, leading to disease progression.

"The approval of osimertinib in the first-line setting represents a major advance in the treatment of patients with EGFR mutations and a significant change in the treatment paradigm," stated Suresh Ramalingam, principal investigator of the FLRUA trial, a researcher with the Winship Cancer Institute of Emory University in Atlanta. "Osimertinib provides robust improvements in progression-free survival with no unexpected safety signals compared to the previous generation of EGFR inhibitors."

Shire notes the announcement made by Takeda (Press release, Shire, APR 19, 2018, View Source [SID1234525813]). The Board of Shire (the "Board") confirms that it has received three conditional proposals from Takeda regarding a possible offer for the Company, on 29 March 2018 (the "First Proposal"), 11 April 2018 (the "Second Proposal") and 13 April 2018 (the "Third Proposal").

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The First Proposal comprised £28 per share in new Takeda shares, to be listed in Japan and in the US through an ADR listing, and £16 per share in cash, representing a potential value of £44 per share and approximately £41 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 50 per cent. of the enlarged Takeda.

Following a thorough review of the First Proposal with its advisers and a Board meeting on 8 April 2018, the Board unanimously rejected the First Proposal, concluding that it significantly undervalued the Company, its growth prospects and pipeline.

The Board has since received two further proposals:

·the Second Proposal comprised £28.75 per share in new Takeda shares, to be listed in Japan and in the US through an ADR listing, and £16.75 per share in cash, representing a potential value of £45.50 per share, only a marginal increase to the First Proposal, and approximately £43 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 51 per cent. of the enlarged Takeda; and

·the Third Proposal also comprised £28.75 per share in new Takeda shares, to be listed in Japan and in the US through an ADR listing, and £17.75 per share in cash, representing a potential value of £46.50 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 51 per cent. of the enlarged Takeda.

The Board met again and thoroughly considered the Third Proposal with its advisers and unanimously rejected it, concluding that it continues to significantly undervalue the Company and Shire’s growth prospects and pipeline.

Following the Board meeting on 14 April 2018 which rejected the Third Proposal, at the Board’s request Shire’s advisers entered into a dialogue with Takeda’s advisers to discuss whether a further, more attractive, proposal may be forthcoming and to understand the basis on which such a proposal would be made.

The Board and management of Shire remain committed to enhancing shareholder value and are focused on fully evaluating internal and external opportunities to maximise value for shareholders, including any further proposals from 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 18, 2018 Kymab Group Limited ("Kymab"), a biopharmaceutical company developing fully human monoclonal antibody therapeutics, reported data on KY1044 (a novel anti-ICOS antibody) and KY1055 (a novel ICOS/PD-L1 bispecific antibody), at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR") Annual meeting held April 14-18, 2018 in Chicago, Illinois, USA (Press release, Kymab, APR 18, 2018, View Source [SID1234537006]).

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The AACR (Free AACR Whitepaper) Annual Meeting covers the latest basic, translational, clinical, and prevention-focused research in the field, including important areas such as early detection, cancer interception, and survivorship in all populations.

Notes to Editors
About Kymab’s AACR (Free AACR Whitepaper) Posters
KY1044 poster

Title: The combination of immune checkpoint blockers with the anti-ICOS KY1044 antibody results in a strong tumour response (#2792)

Session Title: Therapeutic Antibodies, Including Engineered Antibodies 2

Session Date and Time: Monday Apr 16, 2018 1:00 PM – 5:00 PM

Link to the Poster (1.4 Mb PDF)

KY1055 poster

Title: KY1055, a novel ICOS/PD-L1 bispecific antibody, efficiently enhances T cell activation and delivers a potent anti-tumour response in vivo. (#LB-153)

Session Title: Late-Breaking Research: Clinical Research 1

Session Date and Time: Monday Apr 16, 2018 1:00 PM – 5:00 PM

On April 18, 2018 Tusk Therapeutics, an immuno-oncology company focused on developing immune-modulating therapeutics by targeting immune cells in cancer, presented pre-clinical proof-of-concept data generated in collaboration with Cancer Research UK and University College London (UCL), relating to its anti-CD25 programme at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper).

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Tusk Therapeutics presented data on its first-in-class anti-CD25 programme that has entered pre-clinical development. The antibody depletes regulatory T cells (Tregs) while preserving IL-2 binding and signalling on effector T cells (Teffs). Tusk, together with the University College London research group led by Dr. Sergio Quezada, has shown that targeting Tregs with non-IL-2 blocking anti-CD25 antibodies creates highly potent anti-tumour responses in monotherapy and combination therapy. Proof-of-concept has been established in multiple pre-clinical models.

Tregs, a subpopulation of T cells, are key players in the suppressive tumour microenvironment (TME). Tregs in the TME hinder the body’s ability to control the growth of cancerous cells and their presence is correlated with a worse prognosis in multiple cancers. Effective Treg targeting has been a topic in the cancer field for several years and Tusk’s approach demonstrates it is possible to deplete Tregs in solid tumour which leads to tumour control. Tusk’s antibody is specifically selected to preserve signalling of the IL-2 cytokine on effector cells which is a key regulator of immune-activation.

Commenting on the data, Luc Dochez, Chief Executive Officer of Tusk Therapeutics, said: "The data presented at AACR (Free AACR Whitepaper) demonstrate the unique mechanism of action of our anti-CD25 antibody. Unlike existing aCD25 antibodies our antibody has the ability to deplete Tregs without inhibiting effector cell responses. Based on the promising pre-clinical data, we believe that our anti-CD25 candidates will be an ideal combination partner for existing standard of care and immuno-oncology treatments."

​The data was presented as an oral presentation by Dr. Sergio Quezada, Group Leader and Cancer Research UK Senior Research Fellow at The UCL Cancer Institute, and Chairman of Tusk Therapeutics’ Scientific Advisory Board and in two posters, presented by the Tusk and UCL teams. Tusk Therapeutics’ first-in-class anti-CD25 antibody programme was built on novel biology discovered by Tusk Therapeutics in collaboration with Dr. Quezada and his team at UCL. Tusk Therapeutics, Cancer Research UK (via its Commercial Partnerships Team) and UCL announced in 2017, an exclusive licensing and collaboration deal to develop and commercialise antibody-based therapeutics against CD25.