On November 6, 2019 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH; Nasdaq: IPHA) reported that it will provide an update on its preclinical pipeline at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2019 Congress in National Harbor, Maryland, November 6-10, 2019 (Press release, Innate Pharma, NOV 6, 2019, View Source [SID1234550398]). Highlights will include:

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In vivo data on anti-CD39 IPH5201 supporting the rationale for assessing combination with PD-1/PD-L1 checkpoint inhibitors
Preclinical results of anti-CD73 IPH5301 targeting the adenosine immunosuppressive pathway
New generation trifunctional NK cell engagers (NKCEs), supporting its clinical development in immunotherapy
Innate will also present in vitro data on IPH5401, demonstrating that the molecule has the potential to block activation and migration of human neutrophils, a major mechanism to allow for the reactivation of effector cells. The Company believes this data supports its ongoing multi-center, open label, dose-escalation and dose expansion Phase I clinical trial (STELLAR-001), evaluating the safety and efficacy of IPH5401 in combination with durvalumab (anti-PD-L1) in patients with advanced solid tumors.

Eric Vivier, Chief Scientific Officer of Innate Pharma, will also give a presentation on harnessing innate imnunity in cancer, as part of the faculty session dedicated to NK cells.

"We are pleased to present data at SITC (Free SITC Whitepaper) 2019 on several of our preclinical and clinical assets, notably three antibodies targeting the tumor microenvironment, as well as on our new NKCEs technology," commented Eric Vivier, Chief Scientific Officer of Innate Pharma. "These data support the science and innovative technologies our scientists continue to develop, helping to further advance our multi-target strategy in immuno-oncology."

Oral presentation:

– Concurrent Session 312: NK Cells: From Basic Science to Clinical Application "Basic Science" presented by Eric Vivier, DVM, PhD, Innate Pharma
Saturday, November 9 | 5:15 pm

Poster presentations:

– IPH5301, a CD73 blocking antibody targeting the adenosine immunosuppressive pathway for cancer immunotherapy, Poster P323
Friday November 8 | 12:30 – 2 pm & 6:30 – 8 pm

– IPH5201, a blocking antibody targeting the CD39 immunosuppressive pathway, unleashes immune responses in combination with cancer therapies, Poster P488
Saturday November 9 | 12:35 – 2:05 pm & 7 – 8:30 pm

– IPH5401 anti-human C5aR antibody targets suppressive myeloid cells in the TME, Poster P268
Saturday November 9 | 12:35 – 2:05 pm & 7 – 8:30 pm

– Multifunctional natural killer cell engagers targeting NKp46 trigger protective tumor immunity, Poster P776
Saturday November 9 | 12:35 – 2:05 pm & 7 – 8:30 pm

On November 05, 2019 Allogene Therapeutics and Notch Therapeutics reported an exclusive worldwide collaboration and license agreement to research and develop induced pluripotent stem cell (iPSC) AlloCAR therapy products for initial application in non-Hodgkin lymphoma, leukemia and multiple myeloma (Press release, Allogene, NOV 5, 2019, View Source [SID1234618291]). Under the partnership, Allogene and Notch will create allogeneic cell therapy candidates from T cells or natural killer (NK) cells using Notch’s Engineered Thymic Niche (ETN) platform.

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Notch was established in 2018 by Juan Carlos Zúñiga-Pflücker, Ph.D. and Peter Zandstra, Ph.D., recognized pioneers in iPSC and T cell differentiation technology. Notch is developing a next-generation approach to differentiating mature immune cells from iPSCs. The Notch ETN technology platform offers potential flexibility and scalability for the production of stem cell-derived immune cell therapies. iPSCs may provide renewable starting material for AlloCAR T therapies that could allow for improved efficiency of gene editing, greater scalability of supply, product homogeneity and more streamlined manufacturing.

"This collaboration exemplifies Allogene’s long-term commitment to advancing the field of cancer treatment as we continue to expand and progress our innovative pipeline of off-the-shelf AlloCAR candidates," said David Chang, M.D., Ph.D., President, CEO and Co-Founder of Allogene Therapeutics. "The scientific founders of Notch Therapeutics are among the most respected experts in the field of stem cell biology and its applications to generating T cells and other functional immune cells. We are confident that their technology and expertise, combined with Allogene’s leadership in AlloCAR therapies, has the potential to unlock future generations of cell therapy treatments for patients."

"Renewable-source, off-the-shelf cell therapies that may produce cells with greater consistency and at industrial scale have long been the dream for people working in this field," said Ulrik Nielsen, Ph.D., Executive Chairman of Notch. "We are delighted to spring into the research collaboration for iPSC-based AlloCAR therapies with Allogene, a leader in the allogeneic CAR T field, with the goal of expanding options for patients."

Under the terms of the agreement, Notch will be responsible for preclinical research of next-generation iPSC AlloCAR T cells. Allogene will clinically develop the product candidates and holds exclusive worldwide rights to commercialize resulting products. Allogene will provide to Notch an upfront payment of $10 million. Notch will be eligible to receive up to $7.25 million upon achieving certain agreed research milestones, up to $4.0 million per exclusive target upon achieving certain pre-clinical development milestones, and up to $283 million per exclusive target and cell type upon achieving certain clinical, regulatory and commercial milestones as well as tiered royalties on net sales in the mid to high single digits. In addition to this collaboration and license agreement, Allogene has acquired a 25 percent equity position in Notch and will assume a seat on Notch’s Board of Directors.

"Master cell banks of genetically modified, induced pluripotent stem cells could provide an inexhaustible source of cell therapies that may improve outcomes and expand applicability to new areas," said Notch Co-Founder Juan Carlos Zúñiga-Pflücker, Ph.D., a senior scientist at Sunnybrook Research Institute and a Professor and Chair of the Department of Immunology at the University of Toronto.

"This work with Allogene may also pave the way for additional off-the-shelf cell therapeutics that are custom-designed to treat other immunity-related diseases such as infectious diseases, autoimmune diseases and aging," said Notch Co-Founder and Chief Scientific Officer Peter Zandstra, Ph.D., a Professor at the University of British Columbia and University of Toronto.

On November 5, 2019 eFFECTOR Therapeutics, Inc., a leader in the development of selective translation regulators (STRs) for the treatment of cancer, reported the dosing of the first subject in the phase 1/2 study of zotatifin (eFT226) being developed for advanced solid tumor malignancies (Press release, eFFECTOR Therapeutics, NOV 5, 2019, View Source [SID1234553137]). Zotatifin is a novel, potent and selective small molecule inhibitor of eukaryotic initiation factor 4A (eIF4A).

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The study will enroll patients with activating mutations, amplifications or fusions in HER2, ERBB3, FGFR1, or FGFR2 receptor tyrosine kinases, or any KRAS mutation subtype. It will also include pancreatic adenocarcinoma with no molecular typing since the large majority of those patients harbor a KRAS mutation.

"There is an immediate need for more effective treatment options in patients with advanced cancers unable to respond to alternative therapies," said Steve Worland, Ph.D., president and chief executive officer of eFFECTOR. "Tumors treated with agents targeting specific RTKs frequently become resistant, and there are no available therapies targeting multiple KRAS mutation subtypes. The antitumor response observed in preclinical studies demonstrates the potential for zotatifin in the treatment of solid tumors with genetic modifications associated with aggressive disease, including RTK alterations such as FGFR1/2 and HER2 and KRAS, and provides direction for patient selection in our clinical trial."

In the open label, dose escalation and cohort expansion study, subjects will be assigned sequentially to increasing zotatifin doses until the maximum tolerated dose is reached. Zotatifin will be administered as a monotherapy in weekly intravenous infusions in subjects with advanced solid tumor malignancies. Treatment and study subject evaluations will be performed in 21-day cycles.

The primary endpoints of the study include safety and tolerability of zotatifin as monotherapy. Secondary endpoints include antitumor activity and survival, as well as pharmacokinetics of the drug. Exploratory endpoints include pharmacodynamics of zotatifin.

Scientists from eFFECTOR recently presented preclinical data at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) – also known as the Triple Meeting. The data demonstrated that solid tumor cell lines driven by alterations in FGFR1, FGFR2 and HER2 treated with zotatifin showed decreased MAPK and AKT signaling, potent inhibition of cell proliferation and apoptosis and strong in vivo anti-tumor activity, indicating potential for zotatifin to treat FGFR1/2 or HER2-driven cancers.

About Zotatifin (eFT226)

Zotatifin (eFT226) is a potent and selective inhibitor of eukaryotic translation initiation factor 4A (eIF4A). eIF4A is located downstream from key oncogenic mutations and their common resistance mechanisms. Zotatifin inhibits the translation of mRNA encoding several important oncogenes and survival factors, including several RTKS, KRAS, Cyclin D, MCL1 and BCL-2 resulting in potent in vivo efficacy in multiple tumor models dependent on these factors, including colorectal cancer, non-small cell lung cancer, breast cancer, hepatocellular carcinoma and B cell lymphomas. Since Zotatifin inhibits the translation of mRNA encoding KRAS and RTK, it is not limited to any mutation subtypes. The drug is currently being evaluated in a Phase 1/2 clinical trial in patients with solid tumors.

On November 5, 2019 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies for the treatment of cancer, reported that the United States Food and Drug Administration (FDA) has granted AUTO1 orphan drug designation for treatment of acute lymphoblastic leukemia (ALL) patients (Press release, Autolus, NOV 5, 2019, View Source [SID1234550683]).

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According to the National Institute of Health’s National Cancer Institute, in the United States, there will be an estimated 5,930 new cases of ALL and an estimated 1,500 related deaths in 2019. Patients are predominantly children; approximately 60% of cases occur at age < 20 years. ALL occurs when the bone marrow makes too many immature lymphocytes, which are a type of white blood cell. Despite a high rate of response to induction chemotherapy, only 30–40% of adult patients with ALL will achieve long-term remission. Similarly, pediatric patients typically respond well to first-line treatment (combination chemotherapy) but 10 to 20% of total patients relapse with chemotherapy-resistant disease, leading to a significant unmet need in pediatric patients with high-risk relapsed or refractory ALL.

"We are pleased to receive orphan drug designation for AUTO1 for acute lymphoblastic leukemia," said Dr. Christian Itin, chairman and chief executive officer of Autolus. "From the data reported in our ongoing studies, we have seen strong remission rates and excellent CAR T cell expansion and persistence without inducing high-grade CRS, a serious adverse event affecting a significant number of patients on currently available CAR T treatments. We look forward to presenting data on AUTO1 at ASH (Free ASH Whitepaper) at the end of the year."

Orphan drug designation is granted by the FDA Office of Orphan Products Development to drugs and biologics which are intended for the treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S. Under the Orphan Drug Act, the FDA may provide grant funding toward clinical trial costs, tax advantages, FDA user-fee benefits, and seven years of market exclusivity in the United States following marketing approval by the FDA. For more information about orphan designation, please visit the FDA website at www.fda.gov.

About AUTO1
AUTO1 is a CD19 CAR T cell investigational therapy designed to overcome the limitations in safety – while maintaining similar levels of efficacy – compared to current CD19 CAR T cell therapies. Designed to have a fast target binding off-rate to minimize excessive activation of the programmed T cells, AUTO1 may reduce toxicity and be less prone to T cell exhaustion, which could enhance persistence and improve the T cells’ abilities to engage in serial killing of target cancer cells. In 2018, Autolus signed a license agreement under which Autolus acquired global rights from UCL Business plc (UCLB), the technology-transfer company of UCL, to develop and commercialize AUTO1 for the treatment of B cell malignancies. AUTO1 is currently being evaluated in two Phase 1 studies, one in pediatric ALL and one in adult ALL.

On November 5, 2019 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies for the treatment of cancer, announced today pre-clinical data on AUTO6NG, the company’s next generation GD2-targeting CAR T cell therapy, at the 34th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) being held November 6-10, 2019, in Washington, D.C (Press release, Autolus, NOV 5, 2019, View Source [SID1234550682]). SITC (Free SITC Whitepaper) published the abstract today, which can be found at:

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View Source;ABSID=12038&CONF=SITC19&ssoOverride=OFF&CKEY=

"AUTO6NG builds on the clinically active AUTO6 GD2-targeting CAR and adds cell programming modules to improve persistence and render the product insensitive to several tumor defense mechanisms," said Dr Christian Itin, chairman and chief executive officer of Autolus. "This is the first program presentation illustrating our suite of advanced cell programming technologies."

Poster Presentation
Abstract #: P146
Abstract Title: "AUTO6NG: Next generation GD2-targeting CAR T-cell therapy with improved persistence and insensitivity to TGFBeta and checkpoint inhibition for relapsed/refractory neuroblastoma", Achkova, D., et al.
Session Date: Saturday, November 9
Session Time: Posters on display 7:00 am – 8:30 pm Eastern Time; author(s) will be at poster 12:35 – 2:05 p.m. and also during the poster reception 7 – 8:30 p.m.

About AUTO6NG
AUTO6NG is a next generation programmed T cell product candidate in pre-clinical development. AUTO6NG builds on preliminary proof of concept data from AUTO6, a CAR in clinical development for the treatment of neuroblastoma, which can target GD2-expressing cancers with a chimeric antigen receptor (CAR). AUTO6NG incorporates additional cell programming modules to augment its functions by extending persistence and rendering modified T-cells resistant to immune inhibition. With the enhanced properties of AUTO6NG, it may be suitable for the treatment of GD2-expressing solid tumors, including neuroblastoma, osteosarcoma, melanoma, small cell lung cancer, and soft tissue sarcoma.

AUTO6 is currently in a Phase 1 clinical trial for pediatric neuroblastoma conducted by Cancer Research UK in collaboration with University College London. Autolus has worldwide commercial rights to the GD2-targeting programmed T cell product candidate.