On October 9, 2019 Targovax ASA (OSE: TRVX), reported that clinical data on the company’s lead product candidate ONCOS-102, a genetically modified oncolytic adenovirus which has been engineered to selectively infect and replicate in cancer cells, will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting being held November 6-10, 2019, in Maryland, USA (Press release, Targovax, OCT 9, 2019, View Source [SID1234540119]).

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Title:

A pilot study of engineered adenovirus ONCOS-102 in combination with pembrolizumab in checkpoint inhibitor refractory advanced or unresectable melanoma

Authors:

Alexander N. Shoushtari, MD; Anthony J. Olszanski, MD, RPh; Thomas J. Hornyak, MD; Jedd D. Wolchok, MD, PhD; Sylvia Vetrhus; Karianne Risberg Handeland; Lukasz Kuryk, PhD; Magnus Jaderberg, MD;

Date:

9 November 2019

Time:

5:30 pm – 5:45 pm

Presenter:

Dr. Alexander Shoushtari, Principal Investigator, MSKCC, NYC

For further information, please contact:
Renate Birkeli, Investor Relations
Phone: +47-922-61-624
Email: [email protected]

Media and IR enquires:
Andreas Tinglum – Corporate Communications (Norway)
Phone: +47-9300-1773
Email: [email protected]

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On October 8, 2019, Thermo Fisher Scientific Inc. (the "Company") issued $900,000,000 aggregate principal amount of 2.600% Senior Notes due 2029 (the "Notes") in a public offering (the "USD Offering") pursuant to a registration statement on Form S-3 (File No. 333-229951) and a preliminary prospectus supplement and prospectus supplement related to the offering of the Notes, each as previously filed with the Securities and Exchange Commission (the "SEC") (Filing, 8-K, Thermo Fisher Scientific, OCT 8, 2019, View Source [SID1234551119]).

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On September 30, 2019, the Company issued €800,000,000 aggregate principal amount of 0.125% Senior Notes due 2025, €800,000,000 aggregate principal amount of 0.500% Senior Notes due 2028, €900,000,000 aggregate principal amount of 0.875% Senior Notes due 2031, €900,000,000 aggregate principal amount of 1.500% Senior Notes due 2039 and €1,000,000,000 aggregate principal amount of 1.875% Senior Notes due 2049 (the "Euro Offering").

The Notes were issued under an indenture, dated as of November 20, 2009 (the "Base Indenture"), and the Nineteenth Supplemental Indenture, dated as of October 8, 2019 (the "Supplemental Indenture" and, together with the Base Indenture, the "Indenture"), between the Company, as issuer, and The Bank of New York Mellon Trust Company, N.A., as trustee. The sale of the Notes was made pursuant to the terms of an Underwriting Agreement, dated September 24, 2019 (the "Underwriting Agreement"), among the Company, as issuer, and BofA Securities, Inc., Goldman Sachs & Co. LLC, Credit Suisse Securities (USA) LLC and HSBC Securities (USA) Inc., as representatives of the several underwriters named in Schedule A to the Underwriting Agreement. The Underwriting Agreement was separately filed with the SEC on September 25, 2019 as Exhibit 1.2 to the Company’s Current Report on Form 8-K.

The Notes will mature on October 1, 2029. Interest on the Notes will be paid semi-annually in arrears on April 1 and October 1 of each year, beginning on April 1, 2020.

Prior to July 1, 2029 (three months prior to their maturity) (the "Par Call Date"), the Company may redeem the Notes, in whole at any time or in part from time to time, at a redemption price equal to the greater of (1) 100% of the principal amount of the Notes to be redeemed and (2) the sum of the present values of the remaining scheduled payments of principal and interest in respect of the Notes being redeemed (not including any portion of the payments of interest accrued but unpaid as of the date of redemption and assuming that such Notes to be redeemed matured on the Par Call Date), discounted to the date of redemption on a semi-annual basis (assuming a 360-day year of twelve 30-day months), at the Treasury Rate (as defined in the Indenture) plus 15 basis points, plus accrued and unpaid interest on the Notes being redeemed, if any, to, but excluding, the date of redemption.

In addition, on and after the Par Call Date, the Company may redeem some or all of the Notes at a redemption price equal to 100% of the principal amount of the notes to be redeemed, plus accrued and unpaid interest, if any, to, but excluding the date of redemption.

Upon the occurrence of a change of control (as defined in the Indenture) of the Company and a contemporaneous downgrade of the Notes below an investment grade rating by at least two of Moody’s Investors Service, Inc., S&P Global Ratings, a division of S&P Global, Inc., and Fitch Ratings, Limited, the Company will, in certain circumstances, be required to make an offer to purchase the Notes at a price equal to 101% of the principal amount of the Notes, plus any accrued and unpaid interest to, but excluding, the date of repurchase.

The Notes are general unsecured obligations of the Company. The Notes rank equally in right of payment with existing and any future unsecured and unsubordinated indebtedness of the Company and rank senior in right of payment to any existing and future indebtedness of the Company that is subordinated to the Notes. The Notes are also effectively subordinated to any existing and future secured indebtedness of the Company to the extent of the assets securing such indebtedness, and are structurally subordinated to all existing and any future indebtedness and any other liabilities of its subsidiaries.

The Indenture contains limited affirmative and negative covenants of the Company. The negative covenants restrict the ability of the Company and its subsidiaries to incur debt secured by liens on Principal Properties (as defined in the Indenture) or on shares of stock of the Company’s Principal Subsidiaries (as defined in the Indenture) and engage in sale and lease-back transactions with respect to any Principal Property. The Indenture also limits the ability of the Company to merge or consolidate or sell all or substantially all of its assets.

Upon the occurrence of an event of default under the Indenture, which includes payment defaults, defaults in the performance of affirmative and negative covenants, bankruptcy and insolvency related defaults and failure to pay certain indebtedness, the obligations of the Company under the Notes may be accelerated, in which case the entire principal amount of the Notes would be immediately due and payable.

The Company received net proceeds of approximately €4.33 billion from the Euro Offering and expects that the net proceeds from the USD Offering will be approximately $890.68 million, each after deducting the underwriting discount and estimated offering expenses. The Company intends to use the net proceeds of the offerings (together with cash on hand) (i) to repay commercial paper issued to fund the redemption on September 27, 2019 of $300 million aggregate principal amount of 4.70% Senior Notes due 2020 and $800 million aggregate principal amount of 3.15% Senior Notes due 2023 and (ii) to fund the redemption of approximately $4.5 billion aggregate principal amount of outstanding senior notes issued by the Company or its subsidiaries, including all of the outstanding (a) 1.500% Senior Notes due 2020, 4.500% Senior Notes due 2021, 3.600% Senior Notes due 2021 and 3.300% Senior Notes due 2022, each issued by the Company and of which notice was provided to holders on September 30, 2019 and (b) 6.00% Senior Notes due 2020 and 5.00% Senior Notes due 2021 issued by its subsidiary Life Technologies Corporation, of which notice was provided to holders on September 25, 2019.

Wilmer Cutler Pickering Hale and Dorr LLP, U.S. counsel to the Company, has issued an opinion to the Company, dated October 8, 2019, regarding the Notes. A copy of this opinion is filed as Exhibit 5.1 hereto.

The foregoing description of certain of the terms of the Indenture does not purport to be complete and is qualified in its entirety by reference to the full text of each of the Base Indenture and the Supplemental Indenture, which are filed with this report as Exhibits 4.1 and 4.2 hereto, respectively. Each of the foregoing documents is incorporated herein by reference.

On October 8, 2019 GlaxoSmithKline plc reported a five-year collaboration with Lyell Immunopharma, a San Francisco biotechnology company, to develop new technologies to improve cell therapies for cancer patients (Press release, GlaxoSmithKline, OCT 8, 2019, View Source [SID1234540964]). The collaboration will apply Lyell’s technologies to further strengthen GSK’s cell therapy pipeline, including GSK3377794, which targets the NY-ESO-1 antigen that is expressed across multiple cancer types.

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To date, two cell therapies have been approved for blood-borne cancers[1], but engineered T cells have not yet delivered strong clinical activity in common solid tumours. Improving the "fitness" of T cells and delaying the onset of T cell exhaustion could help engineered T cell therapies become more effective. Combining GSK’s strong cell and gene therapy programmes with Lyell’s technologies may allow the joint research team to maximise the activity and specificity of cell therapies in solid tumour cancers, where there is a high unmet medical need.

Dr. Hal Barron, Chief Scientific Officer and President, R&D, GSK said: "We are witnessing significant scientific innovation in cell and gene therapies, transforming the treatment of some blood-borne cancers, but patients with solid tumours are in need of equally effective treatments. Applying Lyell’s novel approach to counter T cell exhaustion and working with world class scientists, such as Rick Klausner and his impressive team, increases our probability of delivering the next generation of cancer cell therapies for patients with solid tumours."

Lyell is exploring several approaches to improving T cell function and increasing T cell "fitness" to enhance initial response rates in solid tumour cancers and to prevent relapses due to loss of T cell functionality. As Lyell addresses inhibition of T cells by the tumour in a fundamental way, there is an opportunity that these technologies can be used as a platform for multiple new cell and gene therapies that can be applied across a broad range of rare and prevalent solid cancers.

Dr. Rick Klausner, founder and CEO, Lyell Immunopharma said: "Our approach is to tackle three of the most significant barriers to T cell efficacy in solid tumours. We are redefining the ways we prepare patient cells to be made into therapies, modulating cells’ functionality so that they maintain activity in the tumour microenvironment, and establishing methods of control to achieve specificity and safety for solid tumour-directed cell therapies."

Lyell has a scientific management team with a long history in the field of immune cell therapy. Rick Klausner is the former head of the National Cancer Institute (NCI) and co-founder of Juno Therapeutics, and whose lab discovered the molecular engine behind T cell receptor and CAR signalling; Stan Riddell, co-founder and the Head of R&D, co-founder of Juno whose pioneering work over three decades at Fred Hutchinson Cancer Research Center has helped to define the parameters of successful adoptive cell therapy; Nick Restifo, EVP of Science, whose research over 25 years at the NCI defined the properties of the T cells capable of therapeutic efficacy in cancer; and Margo Roberts, CSO, whose work in adoptive T cell therapy includes serving as CSO of Yescarta maker Kite Pharma, administering the first CAR T cell into patients in 1993, and demonstrating the role of co-stimulation in T cells for effective CARs.

Next generation engineering that leverages Lyell technologies could further enhance the benefit/risk profile of GSK’s lead programme and other cell therapies in GSK’s pipeline. GSK3377794 uses genetically engineered autologous T cells and is currently in Phase 2, on an accelerated development path.

The collaboration will also build on GSK’s world-leading manufacturing platform and expertise for cell and gene therapy that delivered the world’s first approved ex vivo gene therapy (Strimvelis) for ADA-SCID in 2016. GSK has granted patents and pending patent applications related to its stable cell line technology (SCLT) and has a long-standing collaboration with Miltenyi Biotec to improve quality and scale of output to meet the needs of larger patient populations.

Lyell co-founders also include Crystal Mackall, M.D., who has pioneered work on T cell exhaustion, and David Baker, Ph.D., Director of the University of Washington Institute for Protein Design, whose novel approaches to protein engineering provide technologies to enable enhanced precision, control and safety in cell-based therapies.

Notes to Editors

About GSK’s cell therapy pipeline

GSK has built a pipeline of cell therapy programmes comprising multiple cell platforms and targets including CAR T programmes and an additional TCR T through our existing collaboration with Adaptimmune. While CAR Ts detect cell surface targets, T cell receptor therapies (TCR Ts) detect targets both inside and outside the cancer cells which could expand the number of cancers that could benefit from cell therapies.

GSK3377794 is a NY-ESO-1-directed genetically modified autologous T cell immunotherapy and has been granted PRIME designation by the European Medicines Agency and Breakthrough Therapy Designation by the US Food and Drug Administration based on promising activity in synovial sarcoma. NY-ESO-1 is a cancer target expressed in a wide variety of human cancers.

GSK3377794 has been administered to over 100 patients across multiple cancer types and has shown encouraging activity in synovial sarcoma with a manageable safety profile. Based on this data, GSK is initiating the IGNYTE-ESO pivotal study of GSK3377794 for patients with relapsed/refractory synovial sarcoma, and concurrently exploring the efficacy of GSK3377794 in other cancer types that also express the NY-ESO-1 target, including non-small cell lung cancer, multiple myeloma, and myxoid/round cell liposarcoma.

On October 8, 2019 Galera Therapeutics, Inc., a clinical-stage biopharmaceutical company focused on developing and commercializing a pipeline of novel, proprietary therapeutics that have the potential to transform radiotherapy in cancer, reported final data from its two-year tumor outcomes follow up of patients with locally advanced squamous cell head and neck cancer treated with its lead product candidate, GC4419 (avasopasem manganese) (Press release, Galera Therapeutics, OCT 8, 2019, View Source [SID1234540954]).

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GC4419, a highly selective and potent small molecule dismutase mimetic, is being developed to reduce the incidence and severity of radiation-induced severe oral mucositis (SOM), its lead indication. SOM is a common, debilitating complication of radiotherapy in patients with head and neck cancer. There is currently no FDA-approved drug to treat SOM in patients with head and neck cancer.

As part of its Phase 2b clinical trial of GC4419 in patients with locally advanced head and neck cancer, Galera assessed tumor outcomes of the patients over a two-year period following radiotherapy. Patients in the trial received seven weeks of radiation therapy plus cisplatin, and were treated with either 30 mg or 90 mg of GC4419 or placebo by infusion on the days they received their radiation treatment. At both the one-year interim assessment and final two-year mark, tumor outcomes were maintained across all four measures – overall survival, progression-free survival, locoregional control and metastasis-free survival – in both GC4419 dose groups (30 mg and 90 mg) compared to placebo.

"We are pleased with these data, which demonstrated GC4419, when added to a standard radiotherapy regimen, maintained the efficacy of treatment for head and neck cancer and reduced debilitating radiation-induced oral mucositis," said Mel Sorensen, M.D., President and CEO of Galera Therapeutics. "GC4419 achieved meaningful reductions in the duration, incidence and severity of SOM in the completed Phase 2b trial. These two-year tumor data further reinforce the potential of GC4419 to be a promising treatment to reduce radiation toxicities and complement standard radiotherapy regimens in head and neck cancer."

Full results will be submitted for presentation at a future scientific meeting.

GC4419 is being evaluated in the ongoing pivotal ROMAN Phase 3 trial in patients with head and neck cancer, with topline data anticipated in the first half of 2021. GC4419 is also currently being studied in combination with stereotactic body radiation therapy for its anti-tumor effect in a pilot Phase 1b/2a trial of patients with locally advanced pancreatic cancer.

About GC4419 (Avasopasem Manganese)

Galera’s lead product candidate, GC4419 (avasopasem manganese), is a highly selective and potent small molecule dismutase mimetic that is being developed for the reduction of SOM in patients with head and neck cancer. GC4419 is designed to rapidly convert superoxide to hydrogen peroxide, reducing mucosal damage and thereby the incidence and severity of mucositis. Left untreated, elevated superoxide can damage noncancerous tissues and lead to debilitating side effects, including oral mucositis, which can limit the anti-tumor efficacy of radiation therapy.

GC4419 is being studied in the Phase 3 ROMAN clinical trial of patients with locally advanced head and neck cancer, its lead indication, for its ability to reduce the duration, incidence and severity of radiation-induced severe oral mucositis. In Galera’s 223-patient, double blind, randomized, placebo- controlled Phase 2b clinical trial, GC4419 demonstrated the ability to reduce the median duration of severe oral mucositis (SOM) from 19 days to 1.5 days (92 percent), the incidence of SOM through completion of radiation by 34 percent and the severity of patients’ OM by 47 percent, and GC4419 was well tolerated in the trial when added to a standard radiotherapy regimen. GC4419 is also currently being studied in combination with SBRT for its anti-tumor effect in a pilot Phase 1b/2a trial of patients with locally advanced pancreatic cancer. In addition, in multiple preclinical studies, GC4419 demonstrated an increased tumor response to radiation therapy while preventing toxicity in normal tissue.

The U.S. Food and Drug Administration granted Breakthrough Therapy and Fast Track designations to GC4419 for the reduction of the duration, incidence and severity of SOM induced by radiotherapy in patients with head and neck cancer.

On October 8, 2019 Salarius Pharmaceuticals, Inc. (Nasdaq: SLRX), a clinical-stage oncology company targeting the epigenetic causes of cancers, reported that Memorial Sloan Kettering Cancer Center (MSKCC) in New York City and Nationwide Children’s Hospital (Nationwide Children’s) in Columbus, OH have been added as clinical trial sites in the ongoing Phase 1/2 clinical trial of Seclidemstat for the treatment of Ewing sarcoma (Press release, Flex Pharma, OCT 8, 2019, View Source [SID1234540949]). The addition of MSKCC and Nationwide Children’s brings the total number of active clinical trial sites to eight.

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The Phase 1/2 clinical trial of Seclidemstat in patients with relapsed or refractory Ewing sarcoma is an open-label dose escalation and dose expansion study to determine the maximum tolerated dose (MTD) and establish the initial safety profile of Seclidemstat. The dose expansion portion of the study, or phase 2 portion, may provide potential efficacy data. In September, the Safety Review Committee cleared the third dose level (300 mg Seclidemstat twice-daily), and the fourth dose level is currently enrolling (600 mg Seclidemstat twice-daily). Based on current projections, Salarius expects to reach MTD in early 2020 and report initial patient data later in the same year.

"We are excited to now be working with Memorial Sloan Kettering Cancer Center and Nationwide Children’s Hospital to further develop our lead cancer drug candidate Seclidemstat as a potential treatment for Ewing sarcoma," stated David Arthur, President and Chief Executive Officer of Salarius. "Ewing sarcoma is a rare and devastating pediatric bone and soft-tissue cancer for which there are no targeted treatments currently available. We believe Seclidemstat could have a meaningful impact in Ewing sarcoma as a potential new and less toxic treatment, benefitting patients and their families."

Study enrollment at Memorial Sloan Kettering will be led by Paul A. Meyers, M.D., Chief of Pediatric Sarcoma Service and Vice-Chair for Clinical Affairs. Study enrollment at Nationwide Children’s Hospital will be led by Bhuvana A. Setty, M.D., Nationwide Children’s principal investigator.

In addition to MSKCC and Nationwide Children’s, active clinical trial site locations include, Johns Hopkins All Children’s Hospital in St. Petersburg, FL; Children’s Hospital of Los Angeles in Los Angeles, CA; Moffitt Cancer Center in Tampa, FL; Dana-Farber Cancer Institute in Boston, MA; MD Anderson Cancer Center in Houston, TX; and the Sarcoma Oncology Center in Santa Monica, CA.

More information on the Phase 1/2 clinical trial of Seclidemstat in Ewing sarcoma is available at: View Source