On July 10, 2019 Transgene (Paris:TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of solid tumors, reported it has received the approval from the UK Medicines and Healthcare Products Regulatory Agency (MHRA) to proceed with a Phase 1 clinical trial of its lead myvacTM candidate TG4050 (Press release, Transgene, JUL 10, 2019, View Source [SID1234537466]). TG4050 is being developed as a potential treatment for patients with newly diagnosed, locoregionally advanced, HPV negative, squamous cell carcinoma of the head and neck (SCCHN).

TG4050 is an individualized MVA-based immunotherapy derived from the myvacTM platform. It has been designed to stimulate and educate the patient’s immune system to recognize and destroy tumor cells. Tumor cells accumulate mutations and each patient has a set of mutations that are unique to their tumor. TG4050 has been designed to target a panel of these patient specific mutations, which have been selected using NEC’s Neoantigen Prediction System.

"This trial builds upon a long-term research collaboration in the field of immunology of cancer between Transgene and the University of Southampton. It will allow us to bring a very innovative individualized approach to patients. I expect the study to provide us with data demonstrating the safety and immunogenicity of TG4050. I believe such personalized vaccine approaches are the next paradigm in cancer care and could redefine the way patients with H&N cancer and other solid tumors will be treated" said lead investigator Pr. Christian Ottensmeier, MD, PhD, FRCP, Professor of Experimental Medicine within Medicine at the University of Southampton.

The Phase 1 clinical trial of TG4050 will be carried out in patients with SCCHN that have received an adjuvant (first line) therapy. Antitumor activity of TG4050 as monotherapy will also be measured. This multi-center, open label, two arms trial will include patients in the UK and in France.

The study, sponsored by Transgene, will be co-financed by Transgene and its partner NEC, which will also support the trial by contributing to the therapeutic vaccine design and the selection of target neoantigens (see press release dated March 5, 2019).

Dr. Maud Brandely, MD, PhD, Chief Medical Officer of Transgene commented, "This approval from MHRA follows our recent IND from the FDA in ovarian cancer, allowing us to conduct Phase 1 clinical trials with TG4050 in both the US and Europe. With our partner NEC, we look forward to updating you on the progress on both of these clinical trials. These studies will also provide us with important insights into the optimal way to manufacture this novel individualized immunotherapy which is made specifically for each cancer patient."

TG4050 has also been granted an IND from the US FDA to evaluate TG4050 as a potential treatment for ovarian cancer patients (see press release dated May 13, 2019).

About TG4050
TG4050 is an immunotherapy designed to stimulate the immune system of patients in order to induce a response that is able to recognize and destroy tumor cells in a specific manner.
This personalized immunotherapy is developed for each patient, on the basis of mutations identified through sequencing of tumor tissue, prioritized using NEC’s Neoantigen Prediction System and delivered using the myvacTM technological platform which allows development and manufacture of a product that is specific to each patient and that is within time frames compatible with clinical management.

About myvacTM
myvacTM is a viral vector (MVA) based, individualized immunotherapy platform that has been developed by Transgene to target solid tumors. myvacTM-derived products are designed to stimulate the patient’s immune system, recognize and destroy tumors using the patient’s own cancer specific genetic mutations. Transgene has set up an innovative network that combines bioengineering, digital transformation, established vectorization know-how and unique manufacturing capabilities. Transgene has been awarded an "Investments for the Future" funding from Bpifrance for the development of its platform myvacTM.

About NEC’s Neoantigen Prediction System
NEC’s neoantigen prediction utilizes its proprietary artificial intelligence (AI), such as graph-based relational learning, which is combined with other sources of data to discover candidate neoantigen targets. NEC comprehensively evaluates the candidate neoantigens with a primary focus placed on its in-house MHC-binding affinity prediction. These allow NEC to effectively prioritize the numerous candidate neoantigens identified in a single patient.

On July 10, 2019 Moderna, Inc., (Nasdaq: MRNA) a clinical stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients, reported that Lorence Kim, M.D., Chief Financial Officer will participate in the ROTH RNA Revolution Conference on July 17, 2019 (Press release, Moderna Therapeutics, JUL 10, 2019, View Source [SID1234537465]).

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On July 10, 2019 Horizon Therapeutics plc (Nasdaq: HZNP) reported that Horizon Pharma USA, Inc., its wholly-owned subsidiary, intends, subject to market and other considerations, to offer $500 million aggregate principal amount of senior notes due 2027 (Press release, Horizon Therapeutics, JUL 10, 2019, View Source [SID1234537464]).

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Horizon currently expects to use the net proceeds from the offering, together with approximately $64 million in cash on hand, to redeem $525 million of its outstanding debt, consisting of the outstanding (i) $225 million principal amount of its 6.625% senior notes due 2023 and (ii) $300 million principal amount of its 8.75% senior notes due 2024, as well as to pay the related premiums, and fees and expenses, excluding accrued interest, associated with the redemption. The proposed redemption of Horizon’s existing senior notes is being conducted to further Horizon’s deleveraging strategy, to reduce interest expense and to extend the maturity of its debt obligations to improve its capital structure.

The new senior notes will be fully and unconditionally guaranteed by Horizon, as well as by certain of its existing and future subsidiaries.

The notes will be offered only to persons reasonably believed to be qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the "Securities Act") and to non-U.S. buyers in accordance with Regulation S under the Securities Act. The notes have not been and are not expected to be registered under the Securities Act or under any state securities laws and, unless so registered, may not be offered or sold in the United States or to U.S. persons 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. This press release does not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall it constitute an offer, solicitation or sale in any jurisdiction in which such offer, solicitation or sale is unlawful.

On July 10, 2019 Syndax Pharmaceuticals, Inc. (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported that the U.S. Food and Drug Administration (FDA) has cleared the Company’s Investigational New Drug (IND) application to begin a Phase 1/2 trial for SNDX-5613, a targeted Menin inhibitor, in patients with relapsed/refractory (R/R) acute leukemias (Press release, Syndax, JUL 10, 2019, View Source [SID1234537462]).

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"The FDA’s acceptance of our IND for SNDX-5613 represents an important event in the development of targeted therapies for patients with acute leukemias," said Briggs W. Morrison, M.D., Chief Executive Officer of Syndax. "The advancement of SNDX-5613 builds on three decades of scientific investigation that explored the Menin-MLL-r interaction and its importance in a subset of genetically defined leukemias. Our preclinical results strongly support the therapeutic potential of SNDX-5613 for patients with MLL-r and NPM1 mutant leukemias, many of whom do not derive a durable benefit from existing treatments. We look forward to moving this program into the clinic."

The Phase 1/2 open-label trial will assess orally administered SNDX-5613 in patients with R/R acute leukemias. The Phase 1 portion of the study will assess the safety, tolerability and pharmacokinetics of SNDX-5613, and will seek to establish a recommended Phase 2 dose. The Phase 2 portion will evaluate efficacy, as defined by Complete Remission rate, across three expansion cohorts enrolling adult patients with MLL-rearranged (MLL-r) acute lymphoblastic leukemia (ALL), MLL-r acute myeloid leukemia (AML), and NPM1 mutant AML.

MLL rearrangements occur in approximately 80% of acute leukemia cases in infants and up to 10% of all leukemias. In preclinical models of MLL-r acute leukemias, SNDX-5613 demonstrated robust, dose-dependent inhibition of tumor growth, resulting in a marked survival benefit. Menin-MLL interaction inhibitors have also demonstrated robust treatment benefit in multiple pre-clinical models of NPM1 mutant AML, which represents the most frequent genetic abnormality in adult AML.

About Mixed Lineage Leukemia Rearranged (MLL-r)

Rearrangements of the MLL gene give rise to MLL-r acute leukemias, known to have a poor prognosis, with less than 55% of patients surviving past 5 years. MLL rearrangements produce fusion proteins that require interaction with the protein called Menin to drive leukemic cancer growth. Disruption of the Menin-MLL-r interaction has been shown to halt the growth of MLL-r leukemic cells. MLL-r leukemias, which are routinely diagnosed through currently available cytogenetic or molecular diagnostic techniques, occur in approximately 80% of infant acute leukemias and up to 10% of all acute leukemias. There are currently no approved therapies indicated for MLL-r leukemias.

About NPM1 Mutant Acute Myeloid Leukemia

NPM1 mutant AML, which is distinguished by point mutations in the NPM1 gene that drive the leukemic phenotype, is the most common type of cytogenetically normal adult AML and represents approximately 30% of all adult AML cases. This subtype of AML has a 5-year overall survival rate of approximately 50%. Similar to MLL-r leukemias, NPM1 mutant AML is highly dependent on the expression of specific developmental genes, shown to be negatively impacted by inhibitors of the Menin-MLL interaction. NPM1 mutant AML is routinely diagnosed through currently available screening techniques. There are currently no approved therapies indicated for NPM1 mutant AML.

On July 10, 2019 The U.S. Food and Drug Administration (FDA) reported that it has accepted for review the Biologics License Application (BLA) for isatuximab for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) (Press release, Sanofi Genzyme, JUL 10, 2019, View Source [SID1234537461]). The target action date for the FDA decision is April 30, 2020. Isatuximab is an investigational monoclonal antibody that targets a specific epitope on the CD38 receptor of a plasma cell.

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The BLA is based on positive results from ICARIA-MM, an open-label pivotal Phase 3 clinical trial of isatuximab in patients with RRMM. ICARIA-MM is the first positive randomized Phase 3 trial to evaluate an antibody in combination with pomalidomide and dexamethasone. Results from this trial were presented at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and the 2019 European Society of Hematology (EHA) (Free EHA Whitepaper) Annual Meeting.

Multiple myeloma is the second most common hematologic malignancy[1], affecting more than 138,000[2] people worldwide. Multiple myeloma results in significant disease burden. Patients with multiple myeloma continue to relapse over time making it a difficult to treat and incurable malignancy.

Isatuximab targets a specific epitope on the CD38 receptor. It is designed to trigger multiple, distinct mechanisms of action that are believed to directly promote programmed tumor cell death (apoptosis) and immunomodulatory activity.

Isatuximab received orphan designation for relapsed/refractory multiple myeloma from both the FDA and the European Medicines Agency (EMA), and in the second quarter of 2019 the EMA accepted for review the Marketing Authorization Application.

Isatuximab is currently being evaluated in multiple ongoing Phase 3 clinical trials in combination with current standard treatments for people with relapsed/refractory or newly-diagnosed multiple myeloma. It is also under investigation for the treatment of other hematologic malignancies and solid tumors. Isatuximab is an investigational agent and its safety and efficacy have not been fully evaluated by any regulatory authority.