On June 18, 2020 GlaxoSmithKline plc ("GSK"), acting through its subsidiary GSK Finance (No.3) plc ("the issuer") reported that the issuer has priced $280,336,000 of its senior notes due 2023 ("the notes") exchangeable into ordinary shares of Theravance Biopharma, Inc. ("Theravance Biopharma") currently held by GSK and its affiliates (Press release, GlaxoSmithKline, JUN 18, 2020, View Source [SID1234561209]). The notes will be guaranteed by GSK and will be exchangeable at the option of noteholders on any business day on or after 1 September 2020.

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The notes will mature on 22 June 2023, will not bear interest and will be offered at an issue price 108.5% of their principal amount. The initial exchange rate is 34.4044 shares of Theravance Biopharma ordinary shares per $1,000 principal amount of notes, which is equivalent to an initial exchange price of approximately $29.0660 per share representing a premium of 35% over the volume weighted average price of Theravance Biopharma’s ordinary shares from 9:30 a.m. to 4:00 p.m., New York City time on 17 June 2020. In the aggregate, the notes will be exchangeable into substantially all of the 9,644,807 ordinary shares of Theravance Biopharma currently held by GSK and its affiliates. Upon exchange of the notes, the issuer expects to deliver ordinary shares of Theravance Biopharma but may at its option under certain circumstances, deliver cash or a combination of Theravance Biopharma shares and cash.

The offering is expected to close on 22 June 2020, subject to the satisfaction of customary closing conditions. Theravance Biopharma has agreed to file a shelf registration statement with the U.S. Securities and Exchange Commission (the "SEC") following the completion of the offering to register resales of its ordinary shares deliverable upon exchange of the notes.

GSK expects to use the net proceeds of the offering for general corporate purposes. Theravance Biopharma will not receive any proceeds from the offering.

The offering of the notes has not been registered under the U.S. Securities Act of 1933, as amended (the "Securities Act"), or any state securities laws and, unless so registered, may not be offered or sold in the United States except pursuant to an exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and applicable state securities laws. The notes will be offered by means of an offering memorandum solely to persons reasonably believed to be "qualified institutional buyers" (as that term is defined in Rule 144A under the Securities Act) that are also "qualified purchasers" (within the meaning of Section 2(a)(51) of the U.S. Investment Company Act of 1940, as amended). This press release does not constitute an offer to sell or the solicitation of an offer to buy the notes nor shall there be any sale of notes in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of such state.

This communication is only being distributed to and is only directed at (i) persons who are outside the United Kingdom (the "UK") or (ii) investment professionals falling within Article 19(5) of the Financial Services and Markets Act 2000 (Financial Promotion) Order 2005 (the "Order") or (iii) high net worth companies, and other persons to whom it may lawfully be communicated, falling within Article 49(2)(a) to (d) of the Order (all such persons together being referred to as "relevant persons"). The notes are only available to, and any invitation, offer or agreement to subscribe, purchase or otherwise acquire such notes will be engaged in only with, relevant persons. Any person who is not a relevant person should not act or rely on this document or any of its contents.

PROHIBITION OF SALES TO EEA AND UK RETAIL INVESTORS

The notes are not intended to be offered, sold or otherwise made available to and should not be offered, sold or otherwise made available to any retail investor in the European Economic Area ("EEA") or in the UK. For these purposes, a retail investor means a person who is one (or more) of: (i) a retail client as defined in point (11) of Article 4(1) of Directive 2014/65/EU (as amended, "MiFID II"); or (ii) a customer within the meaning of Directive (EU) 2016/97 (as amended, the "Insurance Distribution Directive"), where that customer would not qualify as a professional client as defined in point (10) of Article 4(1) of MiFID II. Consequently, no key information document required by Regulation (EU) No 1286/2014 (as amended, the "PRIIPs Regulation") for offering or selling the notes or otherwise making them available to retail investors in the EEA or in the UK has been prepared and therefore offering or selling the notes or otherwise making them available to any retail investor in the EEA or in the UK may be unlawful under the PRIIPs Regulation.

On June 18, 2020 Exelixis, Inc. (Nasdaq: EXEL) reported that Michael M. Morrissey, Ph.D., the company’s President and Chief Executive Officer, will participate in a fireside chat as part of the virtual BofA Securities Napa Biopharma Conference on Wednesday, June 24, 2020 at 3:30 PM EDT / 12:30 PM PDT (Press release, Exelixis, JUN 18, 2020, View Source [SID1234561225]).

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To access the webcast link, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company’s website at least 15 minutes prior to the presentation to ensure adequate time for any software download that may be required to listen to the webcast. A replay will also be available at the same location for 14 days.

On June 18, 2020 CDDF reported that provides a neutral platform to stimulate interactions between all stakeholders involved in cancer drug development (Press release, EORTC, JUN 18, 2020, View Source [SID1234561242]). The aim of the organization is to accelerate the delivery of effective oncology agents to patients by encouraging multi-stakeholder discussions.

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The collaboration will foster dialogue on common issues in clinical cancer research especially with other stakeholders. Both organisations intend to organise joint workshops and offer support and endorsement in each other’s events.

"Through the partnership with EORTC, one of the most important academic clinical research organizations worldwide, we believe we are offering unique value to stimulate advancement in oncology treatment and delivery" said Professor Jaap Verweij, CDDF Managing Director. "We believe collaboration is the key to improving outcomes for cancer patients and we look forward to a strong alliance with EORTC that will help identify and overcome challenges in the development and delivery of cancer drugs and deliver swift benefits to cancer patients."

"This is an important partnership for EORTC," said Dr Denis Lacombe, EORTC Director General. "CDDF has been instrumental in discussions with regulators and other stakeholders and with our combined efforts, we can bring challenging issues to the wider oncology community producing effective outcomes."

On June 18, 2020 KinaRx reported that it novel approach to treating lung and thyroid cancers is moving closer to clinical trials.

$399,933 SBIR Phase I grant from the National Cancer Institute to KinaRx, a Purdue University-affiliated startup, will help to advance a novel platform aimed at producing more effective drugs to treat lung and thyroid cancers. The platform targets gene mutations that help cancers grow and expand within the body.

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"Genetic and molecular characterization of cancer-driving kinase mutations has revolutionized the treatment of many types of cancer," said Herman O. Sintim, the Drug Discovery Professor of Chemistry in Purdue’s Department of Chemistry.

KinaRx was founded by Sintim, who is its chief scientific officer, along with M. Javad Aman, Rena Lapidus, Ashkan Emadi, Frederick Holtsberg and Joe O’Neill.

The compounds under development by KinaRx were developed using Sintim’s platform, which rapidly makes complex drug molecules using bioinformatics, multi-component compound synthesis and the understanding of disease biology.

The team has focused on developing novel RET inhibitors, which are compounds designed to target the various cancer cells at work in the body. First-generation RET inhibitors demonstrated about 30% overall response rate (ORR) and no complete regression of tumors. New-generation RET inhibitors in clinical development only showed complete regression of RET-driven tumors in a small subset of patients (2-14%). These poor complete regression rates call for more efficacious RET inhibitors, which are active against drug-resistant mutant RET kinases.

"This Phase I SBIR grant will facilitate several preclinical experiments that are required to advance the novel RET inhibitors into clinical trials," said Sintim, who is a member of the Purdue University Center for Cancer Research and the Purdue Institute for Drug Discovery.

KinaRx has licensed drug compounds through the Purdue Research Foundation Office of Technology Commercialization, which is now located in the Convergence Center for Innovation and Collaboration in Discovery Park District, adjacent to the Purdue campus.

The researchers are looking for partners to continue testing and developing their technology. For more information on licensing and other opportunities, contact Sintim at [email protected].

On June 18, 2020 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biotechnology company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported that its marketing authorization application (MAA) for BRUKINSA (zanubrutinib) for the treatment of patients with Waldenström’s macroglobulinemia (WM) who have received at least one prior therapy or as first-line treatment for patients unsuitable for chemo-immunotherapy has been validated for regulatory review by the European Medicines Agency (EMA) (Press release, BeiGene, JUN 18, 2020, View Source [SID1234561430]).

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"This is our first submission to the EMA and the first for WM, marking a significant milestone for BRUKINSA, which has demonstrated efficacy and clinically meaningful improvements in safety and tolerability in patients with WM compared to the first-generation BTK inhibitor, ibrutinib, in our head-to-head ASPEN trial. BRUKINSA has been approved in the U.S. and China in other indications, and we are excited to continue its broad, global development program to help patients with B-cell lymphomas," said Jane Huang, M.D., Chief Medical Officer, Hematology at BeiGene. "WM is typically a disease of older individuals, and we are hopeful that BRUKINSA’s cardiovascular safety advantages over ibrutinib may help it become a preferred treatment option for patients in Europe with WM."
Clinical data in the MAA include the Phase 3 randomized, open-label, multicenter ASPEN clinical trial (NCT03053440) that evaluated zanubrutinib versus ibrutinib in patients with relapsed/refractory (R/R) or treatment-naïve (TN) WM which was recently presented at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Scientific Program and the 25th European Hematology Association (EHA) (Free EHA Whitepaper) Congress. The safety package in the MAA included pooled safety data from 779 patients with B-cell malignancies treated with BRUKINSA in six clinical trials.
About Waldenström’s Macroglobulinemia (WM)

WM is a rare lymphoma representing approximately 1% of all non-Hodgkin lymphomas and typically progresses slowly after diagnosis.1 In Europe, the estimated incidence of WM is approximately 7 for every 1 million men and 4 for every 1 million women.2
About the Zanubrutinib Clinical Trial Program

Clinical trials of zanubrutinib include:

Fully-enrolled Phase 3 ASPEN clinical trial in patients with Waldenström’s macroglobulinemia (WM) comparing zanubrutinib to ibrutinib (NCT03053440), currently the only approved BTK inhibitor for WM;

Phase 3 SEQUOIA trial comparing zanubrutinib with bendamustine plus rituximab in patients with treatment-naive (TN) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (NCT03336333);

Phase 3 ALPINE trial comparing zanubrutinib to ibrutinib in patients with relapsed/refractory (R/R) CLL/SLL (NCT03734016);

Phase 3 MANGROVE trial comparing zanubrutinib and rituximab to bendamustine and rituximab in patients with untreated mantle cell lymphoma (MCL) (NCT04002297);

Phase 2 MAGNOLIA trial in patients with R/R marginal zone lymphoma (MZL) (NCT03846427);

Phase 2 ROSEWOOD trial (NCT03332017) in China comparing obinutuzumab and zanubrutinib vs obinutuzumab alone in treating patients with R/R FL;

Phase 2 trial (NCT04382586) in the U.S. comparing zanubrutinib plus supportive care to placebo plus supportive care for the treatment of patients with COVID-19 disease and pulmonary distress;

Phase 2 trial (NCT04116437) in the U.S. in patients with previously treated B-cell lymphoma intolerant of prior treatment with ibrutinib and/or acalabrutinib;

Phase 2 trial (NCT03332173) in China in patients with R/R WM; and

Completed Phase 2 trials in China in patients with R/R MCL (NCT03206970) and R/R CLL/SLL (NCT03206918).
About BRUKINSA (zanubrutinib)

BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK), discovered by BeiGene scientists, that is currently being evaluated globally in a broad pivotal clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies.
BRUKINSA was approved by the U.S. FDA to treat adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy on November 14, 2019. This indication was approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
BRUKINSA was approved in China for the treatment of MCL in adult patients who have received at least one prior therapy and CLL/SLL in adult patients who have received at least one prior therapy in June 2020.
BRUKINSA is not approved outside of the United States and China.

IMPORTANT U.S. SAFETY INFORMATION FOR BRUKINSA (ZANUBRUTINIB)

Warnings and Precautions Hemorrhage
Fatal and serious hemorrhagic events have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher bleeding events including intracranial and gastrointestinal hemorrhage, hematuria and hemothorax have been reported in 2% of patients treated with BRUKINSA monotherapy. Bleeding events of any grade, including purpura and petechiae, occurred in 50% of patients treated with BRUKINSA monotherapy.
Bleeding events have occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Co-administration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.
Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.
Infections

Fatal and serious infections (including bacterial, viral, or fungal) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher infections occurred in 23% of patients treated with BRUKINSA monotherapy. The most common Grade 3 or higher infection was pneumonia. Infections due to hepatitis B virus (HBV) reactivation have occurred.
Consider prophylaxis for herpes simplex virus, pneumocystis jiroveci pneumonia and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately.
Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (27%), thrombocytopenia (10%), and anemia (8%) based on laboratory measurements, were reported in patients treated with BRUKINSA monotherapy.
Monitor complete blood counts during treatment and treat using growth factor or transfusions, as needed.

Second Primary Malignancies
Second primary malignancies, including non-skin carcinoma, have occurred in 9% of patients treated with BRUKINSA monotherapy. The most frequent second primary malignancy was skin cancer (basal cell carcinoma and squamous cell carcinoma of skin), reported in 6% of patients. Advise patients to use sun protection.
Cardiac Arrhythmias

Atrial fibrillation and atrial flutter have occurred in 2% of patients treated with BRUKINSA monotherapy. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher events were reported in 0.6% of patients treated with BRUKINSA monotherapy. Monitor signs and symptoms for atrial fibrillation and atrial flutter and manage as appropriate.
Embryo-Fetal Toxicity

Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity, including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for at least 1 week after the last dose. Advise men to avoid fathering a child during treatment and for at least 1 week after the last dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.
Adverse Reactions

The most common adverse reactions in > 10% of patients who received BRUKINSA were neutrophil count decreased (53%), platelet count decreased (39%), upper respiratory tract infection (38%), white blood cell count decreased (30%), hemoglobin decreased (29%), rash (25%), bruising (23%), diarrhea (20%), cough (20%), musculoskeletal pain (19%), pneumonia
(18%), urinary tract infection (13%), hematuria (12%), fatigue (11%), constipation (11%), and hemorrhage (10%). The most frequent serious adverse reactions were pneumonia (11%) and hemorrhage (5%).

Of the 118 patients with MCL treated with BRUKINSA, 8 (7%) patients discontinued treatment due to adverse reactions in the trials. The most frequent adverse reaction leading to treatment discontinuation was pneumonia (3.4%). One (0.8%) patient experienced an adverse reaction leading to dose reduction (hepatitis B).

Drug Interactions

CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily. For co-administration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.
CYP3A Inducers: Avoid co-administration with moderate or strong CYP3A inducers.
Specific Populations

Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily.
INDICATION

BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.
This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.