On December 11, 2019 Ionis Pharmaceuticals, Inc. (the "Company") reported that it entered into separate privately negotiated exchange and/or subscription agreements with certain new investors and certain of the holders of its 1.00% Convertible Senior Notes due 2021 (the "2021 Notes") to exchange $375.6 million in aggregate principal amount of the Company’s 2021 Notes (the "Exchange Transactions") for $439.4 million in aggregate principal amount of the Company’s 0.125% Convertible Senior Notes due 2024 (the "Notes"), and to issue and sell an additional $109.5 million in aggregate principal amount of the Notes (the "Subscription Transactions" and, together with the Exchange Transactions, the "Transactions") (Filing, 8-K, Ionis Pharmaceuticals, DEC 11, 2019, View Source [SID1234552570]).

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On December 19, 2019 and December 20, 2019, the Company issued a total of $548.8 million aggregate principal amount of Notes in the Transactions. The Notes are general unsecured obligations of the Company and bear interest at a fixed rate of 0.125% per year, payable semiannually in arrears on June 15 and December 15 of each year, beginning on June 15, 2020. The Notes are convertible under certain circumstances and may be settled as described below. The conversion rate is initially 12.0075 shares of the Company’s common stock per $1,000 principal amount of Notes (equivalent to an initial conversion price of approximately $83.28 per share of the Company’s common stock). The conversion rate and the corresponding conversion price will be subject to adjustment in some events but will not be adjusted for any accrued and unpaid interest. In addition, if certain corporate events occur prior to the maturity date, the Company will increase the conversion rate for a holder who elects to convert its Notes in connection with such a corporate event in certain circumstances. The Company may not redeem the Notes prior to maturity, and no sinking fund is provided for the Notes. The Notes will mature on December 15, 2024, unless earlier converted or purchased.

The Company did not receive any cash proceeds from the Exchange Transactions. In exchange for issuing the Notes pursuant to the Exchange Transactions, the Company received and cancelled the exchanged 2021 Notes. The Company estimates the net proceeds from the Subscription Transactions were approximately $99.2 million after deducting estimated offering expenses for the Transactions. The Company used a portion of the net cash proceeds from the Subscription Transactions to pay the costs of the previously disclosed convertible note hedge transactions and intends to use the remaining net cash proceeds for general corporate purposes.

Indenture

The Company issued the Notes pursuant to an indenture, dated as of December 19, 2019 (the "Indenture"), by and between the Company and U.S. Bank National Association, as trustee.

Holders of the Notes may convert their Notes at their option at any time prior to the close of business on the business day immediately preceding August 1, 2024 only under the following circumstances: (1) during any calendar quarter commencing after March 31, 2020 (and only during such calendar quarter), if the last reported sale price of the Company’s common stock for at least 20 trading days (whether or not consecutive) during a period of 30 consecutive trading days ending on the last trading day of the immediately preceding calendar quarter is greater than or equal to 130% of the conversion price on each applicable trading day; (2) during the five business day period after any five consecutive trading day period (the "measurement period") in which the trading price per $1,000 principal amount of Notes for each trading day of the measurement period was less than 98% of the product of the last reported sale price of the Company’s common stock and the conversion rate on each such trading day; or (3) upon the occurrence of specified corporate events. On or after August 1, 2024 until the close of business on the second scheduled trading day preceding the maturity date, holders of the Notes may convert their Notes at their option at the conversion rate then in effect at any time irrespective of the foregoing conditions. The Company will settle conversions of Notes by paying and/or delivering, as the case may be, cash, shares of the Company’s common stock, or a combination of cash and shares of the Company’s common stock, at its election, as described in the Indenture.

The Company may not redeem the Notes prior to maturity and no ‘‘sinking fund’’ is provided for the Notes, which means that the Company is not required to redeem or retire the Notes periodically.

If the Company undergoes a fundamental change (as defined in the Indenture), subject to certain conditions, holders of the Notes may require the Company to purchase for cash all or part of their Notes in principal amounts of $1,000 or a multiple thereof, at a purchase price equal to 100% of the principal amount of the Notes to be purchased, plus accrued and unpaid interest to, but excluding, the fundamental change purchase date.

The Notes are the Company’s general unsecured obligations and rank senior in right of payment to any of the Company’s indebtedness that is expressly subordinated in right of payment to the Notes; equal in right of payment with any of the Company’s liabilities that are not so subordinated (including the 2021 Notes); effectively junior in right of payment to any of the Company’s secured indebtedness to the extent of the value of the assets securing such indebtedness; and structurally junior to all indebtedness and other liabilities (including trade payables) of the Company’s subsidiaries.

The events of default, which may result in the acceleration of the maturity of the Notes, include, among other things:

failure to pay interest on the Notes when due and the continuance of such default for a period of 30 days;

failure to pay the principal on the Notes when due;

failure to comply with the Company’s obligation to convert the Notes in accordance with the Indenture upon exercise of a holder’s conversion right and such failure continues for a period of three (3) business days;

failure to provide timely notice of a fundamental change or a specified corporate transaction;

failure by the Company to comply with its obligations under the Notes or the Indenture for a period of 60 days after notice if given in accordance with the Indenture;

certain defaults under loan agreements or other instruments (other than the Indenture) evidencing indebtedness for borrowed money of the Company or any significant subsidiary of the Company in excess of $100 million; and

certain events of bankruptcy or insolvency involving the Company or any significant subsidiary of the Company.

On December 11, 2019 Kazia Therapeutics Limited (ASX: KZA;NASDAQ: KZIA), an Australian oncology-focused biotechnology company, is reported that it’s lead program, GDC-0084, has been selected to join GBM AGILE, an international, academic-led, multi-drug adaptive phase II / III study in glioblastoma (Press release, Kazia Therapeutics, DEC 11, 2019, View Source;iii-study-in-glioblastoma-300972810.html [SID1234552281]). It is expected that data from GBM AGILE will be used to seek marketing approval for GDC-0084 from FDA and other regulatory agencies.

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Key Points

GBM AGILE (NCT03970447) is an adaptive ‘master protocol’ study, in which different drug candidates can be tested for potential use in glioblastoma
Study is designated phase II / III and data from it is considered acceptable for product registration purposes by US FDA
Kazia has entered into a preliminary agreement to commence planning and set-up activities for inclusion of GDC-0084 in GBM AGILE, with a view to commencing recruitment in Q2 / Q3 CY2020, subject to a definitive agreement
Kazia plans to participate in GBM AGILE in place of a company-run registration study, and GBM AGILE will serve as the path-to-market for GDC-0084
Study is expected to recruit up to 200 patients into the GDC-0084 arm
Dr Timothy Cloughesy, GBM AGILE Global Principal Investigator, commented, "We see an urgent need for new therapies in glioblastoma, and GBM AGILE has been designed to provide an opportunity for industry to test new therapeutic agents in a cutting-edge, registration-level study, at considerably lower cost and in a faster time than would typically be possible for a company-driven study. GDC-0084 has the potential to become an important treatment option for brain cancer, and this study is the best way to definitively determine its efficacy in this challenging disease."

GBM AGILE is sponsored and administered by the Global Coalition for Adaptive Research (GCAR), a non-profit organization which includes many of the world’s leading scientists and clinicians in the field of brain cancer (www.gcaresearch.org).

The study commenced recruitment of its first investigational arm in June 2019. GBM AGILE is designed as a ‘master protocol’ study, into which different drug candidates can be placed for testing against a common control arm. It is an ‘adaptive study’, utilizing Bayesian statistical techniques to dynamically adjust the number of patients in a given arm according to emerging signals of activity. This minimizes redundant patient recruitment, saving cost and time. The primary endpoint is overall survival (OS), which is considered the ‘gold standard’ for the approval of new cancer therapies by FDA and other regulatory agencies. Participating drugs are first examined in a stage 1 (phase II) component, which then progresses seamlessly into a stage 2 (phase III) component once pre-defined efficacy hurdles are met.

Dr James Garner, Kazia CEO, commented, "GBM AGILE offers three enormous advantages to Kazia. First, the highly innovative adaptive design allows us to test GDC-0084 in the fastest and most cost-effective way possible. Second, the considerable technical, scientific, and operational capability in GCAR gives us access to resources that we could never hope to draw upon otherwise. Third, the quality of the study, and the caliber of the participating sites, means that GDC-0084 will have the best possible opportunity to demonstrate its potential. No company our size could run a study like this single-handedly, so we have adopted GBM AGILE as our primary path-to-market strategy for GDC-0084."

Dr Garner was speaking from the inaugural International Glioblastoma Drug Development Summit in Boston, MA, where Kazia is an invited speaker. The Summit has convened many of the leading researchers, clinicians, and industry participants in the field of glioblastoma to discuss new approaches to the development of novel therapies.

GBM AGILE has the potential to test new drug candidates in several different patient subgroups. In addition to the newly-diagnosed unmethylated group, which Kazia has already identified as the primary target population, the intent is to also test GDC-0084 in recurrent patients. The company may consider future use in newly-diagnosed methylated patients in consultation with clinicians as further data becomes available.

Kazia and GCAR have entered into a preliminary agreement to begin set-up work for inclusion of GDC-0084 in GBM AGILE, and it is expected that this work will take approximately four to six months. The proceeds of Kazia’s recent institutional financing round will be used to support these activities. Patient recruitment is expected to begin in Q2 / Q3 CY2020, and will be contingent upon execution of a definitive agreement between the parties.

Dr Meredith Buxton, COO of GCAR, added, "The future of drug development requires new approaches, particularly in challenging diseases such as glioblastoma. GBM AGILE is scientifically rigorous, highly efficient, and statistically innovative, and has been designed to provide the best possible platform to generate new treatment options for patients. We look forward to working with the Kazia team to bring GDC-0084 into the study as swiftly as possible."

On December 11, 2019 Northwest Biotherapeutics (OTCQB: NWBO)("NW Bio"), a biotechnology company developing DCVax personalized immune therapies for solid tumor cancers, reported that Dr. Marnix Bosch, Chief Technical Officer of NW Bio, is presenting at 11:40 a.m. today at the inaugural Glioblastoma (GBM) Drug Development Summit being held at the Westin Boston Waterfront Hotel in Boston, Massachusetts (Press release, Northwest Biotherapeutics, DEC 11, 2019, View Source [SID1234552280]).

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The title of Dr. Bosch’s presentation is DCVax-L Phase III Clinical Trial: Development of Dendritic Cell Based Immunotherapies for Cancer — Where Are We, and How Did We Get Here.

The conference is not webcasting the presentations. However, Dr. Bosch’s presentation slides will be made available on NW Bio’s website after the conference session. (www.nwbio.com)

On December 11, 2019 Amgen (NASDAQ:AMGN) reported that its Board of Directors declared a $1.60 per share dividend for the first quarter of 2020 (Press release, Amgen, DEC 11, 2019, View Source [SID1234552279]). The dividend will be paid on March 6, 2020, to all stockholders of record as of the close of business on Feb. 14, 2020. This represents a 10% increase from that paid in each of the previous four quarters. Since the Company initiated a dividend in 2011, it has increased the dividend each year with the quarterly payout in 2019 up more than five-fold since its inception.

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On December 11, 2019 NantHealth, Inc. (NASDAQ: NH), a next-generation, evidence-based, personalized healthcare company, reported new breast cancer research findings presented during a poster session at the San Antonio Breast Cancer Symposium (SABCS) (Press release, NantHealth, DEC 11, 2019, View Source [SID1234552276]).

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The Symposium, held at the Henry B. Gonzalez Convention Center in San Antonio, TX from December 10-14, provides state-of-the-art information on the experimental biology, etiology, prevention, diagnosis and therapy of breast cancer and premalignant breast disease, to an international audience of academic and private physicians and researchers.

NantHealth’s presentation examined how results of the phase 3 KATHERINE clinical trial, first presented at SABCS 2018 and simultaneously published in the New England Journal of Medicine (NEJM), affected treatment patterns and regimen selections among general medical oncologists in the U.S. before and after the results were publicly released. Data from NantHealth’s Eviti Connect, an evidence-based treatment intelligence and web-based oncology decision support platform, was analyzed to determine the rate of requests for treatment authorization for adjuvant Ado-trastuzumab emtansine (T-DM1) in patients with HER2-positive early-stage breast cancer.

Study results indicated an immediate increase in T-DM1 use in the months following SABCS 2018. Based on data pulled from Eviti Connect, 95 cases would have received adjuvant T-DM1 in Q1 2019 after 0 in Q4 2018. When comparing T-DM1 and Trastuzumab use in the adjuvant breast cancer setting for HER2-positive patients, T-DM1 use since December 2018 increased and Trastuzumab use decreased as a percentage of treatment plan requests for adjuvant HER2-positive patients.

"Our research clearly shows that presenting clinical data at a leading conference like the San Antonio Breast Cancer Symposium, and having the data simultaneously published in a medical journal, influences a broad audience of oncologists," said Sandeep "Bobby" Reddy, MD, Chief Medical Officer, NantHealth. "As results indicate an immediate increase in T-DM1 use in the months following SABCS 2018, leveraging multiple communications platforms is an important and effective way to relay practice-changing clinical data to practicing oncologists in the U.S. These forums and supporting scientific journals expose researchers, academics and medical professionals to the latest studies and ideas in the field for which they can apply to their practice."

Title: "Real world data on treatment patterns before and after reporting of the KATHERINE trial: a phase 3 study of adjuvant Ado-trastuzumab emtansine (T-DM1) versus trastuzumab in early stage HER2+ breast cancer"
Authors: Neil Margolis Ph.D., Vlad Kozlovsky, William A. Flood MD, Sandeep K. Reddy MD
Poster Session and Number: Session 1, P1-15-08
Location: Henry B. Gonzalez Convention Center
Date and Time: Wednesday, December 11, 2019 (5:00 PM – 7:00 PM CT)

"As cancer therapies become more complex, Eviti was designed to help oncologists validate cancer treatment options and align all parties around value-based oncological care. Defining the appropriate regimens for patients is essential, and studies like this are an effective way to communicate how medical meetings and peer-reviewed journals are a valuable and timely way to get information to physicians," said Dr. William A. Flood, CMO of Eviti.