On November 18, 2021 Exact Therapeutics AS ("EXACT-Tx", or "the Company" Euronext Growth: EXTX), a clinical-stage precision health company evaluating Acoustic Cluster Therapy (ACT) across multiple therapeutic areas, reported a number of strategic, operational and scientific developments (Press release, Exact Therapeutics, NOV 18, 2021, View Source [SID1234595791]).

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As reported in May 2021, EXACT-Tx plans to file a protocol amendment regarding its ACTIVATE phase 1 clinical trial with the UK MHRA. Following approval, the Company plans to recommence enrolment in the trial at the Royal Marsden Hospital London / Institute of Cancer Research with the recruitment of patients in the part 1 cohort planned to be completed by mid 2022. The study aims to evaluate the combination of PS101 ACT with standard of care chemotherapy for treatment of liver metastases in patients with metastatic colorectal cancer A number of valuable and encouraging insights have been gained from this first cohort of treated patients particularly with respect to the application of ultrasound.

The Company also announces that it aims to start its first clinical trial in the USA to evaluate ACT in pancreatic cancer patients. In the USA there are approximately 60,000 newly diagnosed cases of pancreatic cancer and approx. 50,000 deaths per year. The Company expects to submit IND filing to the FDA by mid 2022 which, if approved, will be followed by the start of the clinical trial towards the end of 2022. Today, the 18th of November, is Pancreatic Cancer Awareness Day, and EXACT-Tx is committed to play its role in fighting this aggressive disease.

EXACT-Tx is pleased to announce that Co-Founder Dr Andrew ("Andy") Healey has returned to the Company as Chief Scientific Officer. Andy brings over 20 years experience in the life sciences industry, primarily working with contrast agents and optical molecular imaging, physics, instrumentation, characterisation and clinical imaging systems & trials. The Company’s management team has been significantly strengthened this year with the appointments of Dr Hilary McElwaine-Johnn as Chief Medical Officer and Dominic Moreland as Chief Financial Officer and subsequently Interim Chief Executive Officer.

Strong preclinical data on ACT were recently published in The Journal of Controlled Release 1 which demonstrated that ACT safely and temporarily increased the permeability of the Blood Brain Barrier ("BBB") in animal models as well as increased the penetration and accumulation of co-administered compounds including nanoparticles with no treatment related tissue damage observed. The BBB remains a formidable challenge to the delivery of drugs into the brain. The published preclinical data demonstrates that ACT could be a potential strategy to overcome this obstacle and promote efficient and specific crossing through BBB of therapeutically relevant agents, addressing a huge unmet medical need and further demonstrating the power of the ACT platform. "We have demonstrated that ACT has the ability to open the BBB in a pre-clinical model to deliver large molecules and nano particles with no observable damage to the brain. This approach is an exciting and evolving field that has the promise to deliver drug and to treat the central nervous system." says Professor Catharina de Lange Davies, Dept. of Physics, Norwegian University of Science and Technology (NTNU), and co-author of the paper.

Dr Masha Strømme, Executive Chair of the Board, stated: "We have significantly strengthened our team over the last few months and are well positioned to maximise the value of our innovative Acoustic Cluster Therapy (ACT) platform for ultrasound enhanced drug targeting which has the potential to significantly amplify the clinical utility of a wide range of therapeutic agents across most drug classes and improve upon standard of care. I am very pleased to welcome Andy whose technical expertise and industry know-how coupled with his longstanding commitment to EXACT-Tx is a very strong addition to the leadership team. I look forward to working with him again as we further investigate this exciting approach to ultrasound mediated therapeutic targeting."

On November 18, 2021 Cytovia Therapeutics, Inc., a biopharmaceutical company developing allogeneic "off-the-shelf" gene-edited iNK (NK cells derived from iPSC) and CAR (Chimeric Antigen Receptor) Natural Killer (NK) cells derived from induced pluripotent stem cells (iPSCs) and Flex-NK cell engager multifunctional antibodies, and Cellectis (Euronext Growth: ALCLS – Nasdaq: CLLS), a clinical-stage gene-editing company employing its core technology to develop products based on gene-editing with a portfolio of allogeneic chimeric antigen receptor (CAR-)T cells in the field of immuno-oncology and gene-edited hematopoietic stem cells in other indications, reported that they have expanded their collaboration of TALEN gene-edited iPSC-derived NK and CAR-NK cells to include new CAR target and development in China by Cytovia’s joint venture entity, CytoLynx Therapeutics (Press release, Cellectis, NOV 18, 2021, View Source [SID1234595789]).

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The amended financial terms include an equity stake totaling $20 million in Cytovia stock as well as up to $805 million of development, regulatory, and sales milestones and single-digit royalty payments on the net sales of all partnered products commercialized by Cytovia.

"We are pleased to expand the collaboration with Cellectis to enable Cytovia to develop iNK products that will leverage the high-precision of TALEN to perform gene-editing to minimize the risk of off-target effects and unlock the full potential of NK cells as a first line of defense against cancer. Cytovia’s internal research and development, and manufacturing teams are actively developing multiple gene-edited therapeutic candidates and optimizing our technology platform towards next generation products," said Dr. Daniel Teper, Chairman & CEO of Cytovia Therapeutics.

Cellectis is developing custom TALEN, which Cytovia uses to edit iPSCs. Cytovia is responsible for the differentiation and expansion of the gene-edited iPSC master cell bank into NK cells and is conducting the pre-clinical evaluation, clinical development, and commercialization of the mutually-agreed-upon selected therapeutic candidates. Cellectis is granting Cytovia a worldwide license under the patent rights over which Cellectis has the control in this field, including in China, enabling Cytovia to modify NK cells to address multiple gene-targets for therapeutic use in several cancer indications.

"We are thrilled at the progress Cytovia has accomplished in the past year," said Dr. André Choulika, CEO of Cellectis. "Cytovia has attracted a world-class scientific team and is advancing its clinical candidates in areas of significant unmet medical need, sharing Cellectis’ mission to provide life-saving off-the-shelf allogeneic cell therapy to patients."

On November 18, 2021 RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, reported an underwritten public offering of American Depositary Shares ("ADSs") (Press release, RedHill Biopharma, NOV 18, 2021, View Source [SID1234595788]). Each ADS represents ten ordinary shares, par value NIS 0.01 per share, of the Company. All of the ADSs to be sold in the offering will be offered by RedHill. RedHill has granted the underwriter a 30-day option to purchase up to an additional 15 percent of the number of ADSs offered in the public offering.

Cantor Fitzgerald & Co. is acting as sole bookrunner for the proposed offering.

RedHill intends to use the net proceeds of the offering to fund its commercialization activities, clinical development programs and for acquisitions and general corporate purposes.

The securities described above will be offered by RedHill pursuant to a shelf registration statement on Form S-3 (No. 333-232777) declared effective by the Securities and Exchange Commission (the "SEC") on August 8, 2019.

The securities will be offered only by means of a prospectus supplement and accompanying prospectus relating to the offering that form a part of the registration statement. A preliminary prospectus supplement and the accompanying prospectus relating to and describing the terms of the offering will be filed with the SEC and will be available on the SEC’s website at View Source Copies of the preliminary prospectus supplement, when available, and the accompanying prospectus relating to the offering may be obtained from Cantor Fitzgerald & Co., 499 Park Avenue, 4th Floor, New York, New York 10022, Attn: Capital Markets Department, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

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On November 18, 2021, Thermo Fisher Scientific (Finance I) B.V. ("Thermo Fisher International"), an indirect, wholly-owned finance subsidiary of Thermo Fisher Scientific Inc. (the "Company"), reported that issued €1,700,000,000 aggregate principal amount of Floating Rate Senior Notes due 2023 (the "Floating Rate Notes"), €550,000,000 aggregate principal amount of 0.000% Senior Notes due 2023 (the "2023 Notes") and €550,000,000 aggregate principal amount of 0.000% Senior Notes due 2025 (the "Sustainability Notes", and, together with the Floating Rate Notes and the 2023 Notes, the "Notes") in a public offering (the "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, NOV 18, 2021, View Source [SID1234595787]). The Company has fully and unconditionally guaranteed the Notes on a senior unsecured basis (the "Guarantee" and, together with the Notes, the "Securities").

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The Securities were issued under an indenture, dated as of August 9, 2016 (the "Base Indenture"), and the Fourth Supplemental Indenture, dated as of November 18, 2021 (the "Supplemental Indenture" and, together with the Base Indenture, the "Indenture"), among Thermo Fisher International, as issuer, the Company, as guarantor, and The Bank of New York Mellon Trust Company, N.A., as trustee.

The Floating Rate Notes will mature on November 18, 2023, the 2023 Notes will mature on November 18, 2023 and the Sustainability Notes will mature on November 18, 2025. Interest on the Floating Rate Notes will be paid quarterly in arrears on February 18, May 18, August 18 and November 18 of each year, commencing on February 18, 2022.

Prior to October 18, 2025, in the case of the Sustainability Notes, and at any time, in the case of the 2023 Notes, Thermo Fisher International may redeem such series of 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 (assuming, with respect to the Sustainability Notes, that the Sustainability Notes to be redeemed matured on October 18, 2025), discounted to the date of redemption on an annual basis (ACTUAL/ACTUAL (ICMA)), using a discount rate equal to the Comparable Bond Rate (as defined in the Indenture) plus, in each case, 10 basis points, plus, in each case, accrued and unpaid interest on the Notes being redeemed, if any, to, but excluding, the date of redemption.

In addition, on and after October 18, 2025, the Company may redeem the Sustainability Notes, in whole at any time or in part from time to time, at a redemption price equal to 100% of the principal amount of the Sustainability 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, Thermo Fisher International 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 accrued and unpaid interest, if any, to, but excluding, the date of repurchase.

The Notes are general unsecured obligations of Thermo Fisher International. The Notes rank equally in right of payment with existing and any future unsecured and unsubordinated indebtedness of Thermo Fisher International and rank senior in right of payment to any existing and future indebtedness of Thermo Fisher International that is subordinated to the Notes. The Notes are also effectively subordinated to any existing and future secured indebtedness of Thermo Fisher International 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 Guarantee is a general unsecured obligation of the Company. The Guarantee ranks equally in right of payment with existing and any future unsecured and unsubordinated indebtedness of the Company and will rank senior in right of payment to any existing and future indebtedness of the Company that is subordinated to the Guarantee. The Guarantee is also effectively subordinated to any existing and future secured indebtedness of the Company to the extent of the assets securing such indebtedness, and is structurally subordinated to all existing and any future indebtedness and any other liabilities of its subsidiaries (other than, with respect to Thermo Fisher International, the Notes).

The Indenture contains limited affirmative and negative covenants of the Company and Thermo Fisher International. 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 each of the Company and Thermo Fisher International to merge or consolidate or sell all or substantially all of their respective 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 Thermo Fisher International under the Notes may be accelerated, in which case the entire principal amount of the Notes would be immediately due and payable.

Wilmer Cutler Pickering Hale and Dorr LLP, U.S. counsel to the Company and Thermo Fisher International, has issued an opinion to the Company and Thermo Fisher International, dated November 18, 2021, regarding the legality of the Securities, and Linklaters LLP, Dutch counsel to Thermo Fisher International, has issued an opinion to Thermo Fisher International, dated November 18, 2021, regarding the Notes. Copies of these opinions are filed as Exhibits 5.1 and 5.2 hereto, respectively.

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 November 18, 2021 Immunomic Therapeutics, Inc. (‘ITI’), a privately-held clinical stage biotechnology company pioneering the study of nucleic acid immunotherapy platforms, reported that Kristen Batich, MD, Ph.D. and a team from Duke University School of Medicine will present clinical data at the 2021 Society for Neuro-Oncology (SNO) Annual Meeting being held in Boston, MA, November 18-21st, 2021 (Press release, Immunomic Therapeutics, NOV 18, 2021, View Source [SID1234595786]).

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The data to be presented at the SNO meeting are from three sequential clinical trials utilizing Cytomegalovirus (CMV)–specific dendritic cell vaccines that encode the chimeric CMV protein LAMP-pp65 in patients with primary Glioblastoma. The patients were given serial vaccination through adjuvant temozolomide cycles. The Phase II ATTAC study (NCT00639639) led to an expanded cohort trial (ATTAC-GM: NCT00693639) resulting in positive immunologic and clinical response. The larger confirmatory trial, ELEVATE (NCT02366728), revealed significantly longer overall survival (OS) in patients randomized to LAMP pp65 RNA loaded DC vaccines combined with tetanus-diphtheria booster. The results demonstrate that a CMV pp65-LAMP RNA-pulsed dendritic cell vaccination was associated with positive immunologic and clinical response in patients with glioblastoma (GBM).

"The clinical data to be presented demonstrates the potential impact of our UNITE technology platform, powered by LAMP, and will help validate our therapeutic approach utilizing vaccines to treat difficult cancers like glioblastoma," said Dr. Teri Heiland, Chief Scientific Officer of Immunomic Therapeutics, Inc. "We are encouraged by the immunological response shown with this patient group and we look forward to Dr. Batich’s presentation of these positive findings at the SNO meeting."

Abstract Session: Clinical Trials I

Title: Reproducibility of clinical trials using CMV-targeted dendritic cell vaccines in patients with glioblastoma
Category: CTIM-10
Date and Time: Friday, November 19, 2021 4:45 PM – 4:50 PM EST
Location: Ballroom C, Hynes Convention Center, Boston, MA

Presenter:

Kristen A. Batich, MD, PhD
Duke University Medical Center
Durham, United States

About ITI-1000 and the Phase 2 (ATTAC-II) Study

ITI-1000 is an investigational dendritic cell vaccine therapy currently in a Phase 2 clinical trial (ATTAC-II) for the treatment of GBM. ITI-1000 was developed using Immunomic’s proprietary investigational lysosomal targeting technology, UNITE, in the context of cell therapy. In May 2017, Immunomic exclusively licensed a patent portfolio from Annias Immunotherapeutics for use in combination with UNITE and ITI-1000, allowing Immunomic to combine UNITE with a patented and proprietary CMV immunotherapy platform. The ATTAC-II study (NCT02465268) is a Phase II randomized, placebo-controlled clinical trial enrolling patients with newly diagnosed GBM that will explore whether dendritic cell (DC) vaccines, including ITI-1000, targeting the CMV antigen pp65 improve survival. This study is enrolling up to 120 subjects at 3 clinical sites in the United States. For more information on the ATTAC-II study, please visit www.clinicaltrials.gov.

About UNITE

ITI’s investigational UNITE platform, or UNiversal Intracellular Targeted Expression, works by fusing pathogenic antigens with the Lysosomal Associated Membrane Protein 1 (LAMP-1), an endogenous protein in humans, for immune processing. In this way, ITI’s vaccines (DNA or RNA) have the potential to utilize the body’s natural biochemistry to develop a broad immune response including antibody production, cytokine release and critical immunological memory. This approach puts UNITE technology at the crossroads of immunotherapies in a number of illnesses, including cancer, allergy and infectious diseases. UNITE is currently being employed in a Phase II clinical trial as a cancer immunotherapy. ITI is also collaborating with academic centers and biotechnology companies to study the use of UNITE in cancer types of high mortality, including cases where there are limited treatment options like glioblastoma and acute myeloid leukemia. ITI believes that these early clinical studies may provide a proof of concept for UNITE therapy in cancer, and if successful, set the stage for future studies, including combinations in these tumor types and others. Preclinical data is currently being developed to explore whether LAMP-1 nucleic acid constructs may amplify and activate the immune response in highly immunogenic tumor types and be used to create immune responses to tumor types that otherwise do not provoke an immune response.