On March , 2019 Sumitomo Dainippon Pharma Co., Ltd. (Head Office: Osaka, Japan; Representative Director, President and CEO: Hiroshi Nomura hereinafter called "Sumitomo Dainippon Pharma") reported that it received approval in Japan for "RETHIO for Intravenous Infusion 100 mg" (generic name: thiotepa, hereinafter called "RETHIO") in Japan on March 26, for conditioning treatment prior to autologous hematopoietic stem cell transplantation (auto-HSCT) for pediatric malignant solid tumors (Press release, Sumitomo Dainippon Pharma, MAR 26, 2019, View Source [SID1234605563]). Sumitomo Dainippon Pharma will launch the product after NHI drug price listing.

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Thiotepa is an antitumor alkylating agent that belongs to the ethyleneimine group and inhibits DNA synthesis. In Japan, Sumitomo Chemical Co., Ltd. launched this agent as Tespamin injection in 1958, which was then taken over by Sumitomo Pharmaceuticals Co., Ltd. (current Sumitomo Dainippon Pharma) in 1984. However, following the discontinued provision of its active pharmaceutical ingredients in 2006, Sumitomo Dainippon Pharma discontinued manufacturing of Tespamin in 2009, and its marketing authorization was withdrawn in 2010. This agent has not been available since then in Japan.

After the discontinuation of its marketing in Japan, many requests for its use for this indication were made by academic societies and patient advocacy groups concerned, as thiotepa was approved for the indication in Europe in 2010. In response, the Evaluation Committee on Unapproved or Off-labeled Drugs with High Medical Needs of the Ministry of Health, Labour and Welfare of Japan (MHLW) determined that the medical need for thiotepa was high. Accordingly, the MHLW invited pharmaceutical companies to develop the agent for the indication, to which Sumitomo Dainippon Pharma replied in September 2013 and initiated a Phase 1 study in Japan from November 2016 as a pharmacokinetic study, the results of which were included in the data attached to the application in July 2018. Meanwhile, Sumitomo Dainippon Pharma is also preparing an application for approval of RETHIO for indication of conditioning treatment prior to auto-HSCT for malignant lymphoma.

Sumitomo Dainippon Pharma expects that the approval would provide a new therapeutic option for patients in areas with high unmet medical needs, such as conditioning treatment prior to auto-HSCT for pediatric malignant solid tumors, contributing to the treatment of patients with such symptoms.

About autologous hematopoietic stem cell transplantation (auto-HSCT)
Autologous hematopoietic stem cell transplantation is a therapy that aims to reconstruct hematopoietic capacity via intravenous transfusion of normal hematopoietic stem cells of the patient himself/herself after eradicating intractable cancers by conditioning myeloablative treatment prior to transplantation using maximum levels of anti-cancer drugs or radiation. Unlike allogeneic hematopoietic stem cell transplantation that uses donor’s hematopoietic stem cells, auto-HSCT is free from concerns about immunoreactions by transplanted hematopoietic stem cell-derived immune cells against host. As such, this conditioning treatment prior to auto-HSCT aims to eradicate tumor cells as much as possible through high-dose chemotherapy using anticancer drugs at doses that exceed the maximum tolerated level for bone marrow. According to the Japanese Data Center for Hematopoietic Cell Transplantation, the number of cases of hematopoietic stem cell transplantation in Japan totaled 93,902 between 1986 and 2016, among which 33,527 cases were autologous hematopoietic stem cell transplantation.

About pediatric malignant solid tumors
According to the Practical guidelines for pediatric cancer 2016, approximately 2,500 new cases of pediatric cancer occur annually in Japan. According to the Japanese Society of Pediatric Hematology/Oncology, 904 cases of solid tumors excluding hematopoietic organ tumors, such as leukemia, are registered in 2015. Compared to solid tumors in adults, pediatric malignant solid tumors are shown to be relatively chemosensitive. As a result, better outcome of high-dose chemotherapy combined with hematopoietic stem cell transplantation is expected, and transplantation is now being performed as a part of daily clinical practice. According to the Japanese Data Center for Hematopoietic Cell Transplantation, the number of hematopoietic stem cell transplantations for pediatric solid tumor, including pediatric malignant solid tumor, patients totaled 3,276 between 1991 and 2016, among which 3,058 cases were auto-HSCT.

About the Evaluation Committee on Unapproved or Off-labeled Drugs with High Medical Needs
The Evaluation Committee on Unapproved or Off-label Drugs with High Medical Needs is a committee established to promote the development of unapproved or off-label drugs by pharmaceutical companies that are approved for use in Europe and the United States, etc., but not approved in Japan. It is organized under the Ministry of Health, Labour and Welfare of Japan and consists of academic experts in medical and pharmaceutical fields.

On March 26, 2019 Akrevia Therapeutics, a privately held biopharmaceutical company focused on developing highly-potent, tumor-targeted immuno-oncology therapeutics, and City of Hope, an independent research and treatment center for cancer, diabetes and other life-threatening diseases, reported that they have entered into an exclusive licensing agreement that will allow Akrevia to utilize innovative technology to engineer potent immune-activating cytokines that can be selectively activated in the tumor microenvironment (Press release, Akrevia Therapeutics, MAR 26, 2019, View Source [SID1234554019]).

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The tumor microenvironment has distinct physiological characteristics that can be exploited to help develop tools to deliver therapies that are more precise and potent than existing treatments. The new technology, licensed from the lab of John Williams, Ph.D., at City of Hope, is suited to a broad spectrum of cytokines – molecules for which current tumor activation approaches are not applicable. This novel Switchblade allows inactivated proteins to "flick open" at the point of attack, releasing potent anti-tumor agents precisely where they are needed, thus maximizing efficacy and minimizing the peripheral side effects that limit current cytokine therapies. This new platform can be applied to other highly potent biologic architectures, including diverse cytokine family members, chemokines and agonistic immune modulators which to date have proved intractable in clinical development. This new technology will augment Akrevia’s existing Aklusion platform technologies, and augments the existing technology previously licensed from City of Hope.

"Cytokines have immense promise as highly potent cancer immunotherapeutics, with well-understood biology – but their extreme potency and lack of tumor targeting have thwarted attempts to exploit this clinically," said Tim Clackson, Ph.D., president and executive vice president, R&D, Akrevia Therapeutics. "The new technology licensed from City of Hope will substantially complement our current platform portfolio, providing the ability to target tumor activation of the full range of potent, immune-stimulating molecules. Akrevia will use the newly licensed technology to aggressively advance our pipeline and build towards the next generation of targeted cancer treatments."

Under the agreement, Akrevia gains exclusive commercial rights for application of the technology to the development of proprietary products. City of Hope, internationally recognized for pioneering technology that enabled the creation of numerous breakthrough cancer drugs, developed this technology to help investigators and researchers shield their selected antibodies for targeted therapies and to improve drug delivery. The nonprofit institution is working to improve precision medicine for all patients.

"At City of Hope, our research teams focus on rapidly developing technologies that can quickly move from laboratory research to clinical treatment," said Williams, professor of Molecular Medicine, City of Hope. "Our team has developed a novel approach to unlock the potential of multiple important immuno-oncology mechanisms to deliver potent, targeted agents to patients. We look forward to our continued collaboration with Akrevia to harness the therapeutic potential of this technology with the goal of improving treatment for patients."

On March 26, 2019 OSE Immunotherapeutics (ISIN: FR0012127173; Mnémo: OSE), reported a new research collaboration agreement with premier cancer research hospital, Léon Bérard Cancer Center in Lyon, France, to use artificial intelligence (AI)-based bioanalysis and bioinformatics to identify novel targets in immuno-oncology (Press release, OSE Immunotherapeutics, MAR 26, 2019, View Source [SID1234553881]).

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Léon Bérard Cancer Center (CLB) has both a cancer immunotherapy laboratory and translational research laboratory and is recognized as a scientific expert in oncology, particularly in tumor targeting and in the immune environment. Additional resources at CLB include its state-of-the-art bioinformatics platform and biological resource center. Their experience in analyzing and integrating data from The Cancer Genome Atlas (TCGA) allows detailed analysis of clinically relevant targets in populations that could potentially benefit from an innovative therapeutic approach.

This new collaborative immuno-oncology research program will use different patient cohorts and tumor biopsies to identify novel molecular targets associated with the primary and secondary resistance to
PD-1/PD-L1 immune checkpoint inhibitors and to validate a strategy of combining drugs based on target expression profile.

The research is based on an artificial intelligence approach jointly developed which will be applied to analyze gene expression in the human tumor microenvironment and the composition of tumor infiltrates. The findings from this collaboration will be used for the selection and validation of innovative targets for early development of new drug candidates from the platform of bispecific fusion proteins targeting PD-1 and innovative targets (BiCKI).

"We are very excited to begin a new collaboration with an expert team and the CLB, a premier cancer research center. The goal of this partnership is to identify and validate new targets that will help streamline the development of new treatment approaches for cancer, especially in difficult to treat tumors," said Alexis Peyroles, chief executive officer of OSE Immunotherapeutics.

Professor Jean-Yves Blay, M.D., Ph.D., director of the Léon Bérard Cancer Center commented, "Our AI approach combined with our translational and immunological research platforms will enable us to analyse tumor immune parameters and to identify potential new pathways to address unmet needs for cancer patients. This partnership brings together top experts in oncology research and translational science with the hopes of rapidly advancing the discovery of first-class treatment options for cancer patients. We are very pleased to work in collaboration on this cutting-edge research with OSE Immunotherapeutics."

On March 26, 2019 Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical-stage biotechnology company focused on discovering and developing novel small molecule drugs for the treatment of cancer and other life-threatening diseases, reported that the first patient has been treated in the Phase 1/2 open-label clinical trial of the glutaminase inhibitor telaglenastat (CB-839) in combination with Pfizer’s poly adenosine diphosphate ribose polymerase (PARP) inhibitor talazoparib, also known as Talzenna , in patients with advanced or metastatic solid tumors (Press release, Calithera Biosciences, MAR 26, 2019, View Source [SID1234535225]).

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"The initiation of this clinical trial of telaglenastat in combination with talazoparib marks the first of two clinical trials that will evaluate telaglenastat with approved Pfizer therapeutics as part of this collaboration," said Susan Molineaux, PhD, president and chief executive officer of Calithera. "We believe these new combination trials have the potential to broaden the opportunities for telaglenastat to improve patient outcomes."

Preclinical studies have shown that telaglenastat synergizes with PARP inhibitors to impair DNA synthesis, enhance DNA damage and block cancer cell proliferation. The combination of telaglenastat with PARP inhibitors has demonstrated synergistic activity in a number of preclinical cancer models, including renal cell carcinoma (RCC), triple negative breast cancer (TNBC), colorectal cancer (CRC), non-small cell lung cancer (NSCLC), ovarian cancer and prostate cancer. In October 2018, Calithera entered into a clinical trial collaboration agreement with Pfizer to evaluate telaglenastat in two clinical trials. The first trial is a combination of telaglenastat with talazoparib and the second trial is a combination of telaglenastat with palbociclib, also known as Ibrance. As part of this agreement, Pfizer will provide palbociclib and talazoparib, as well as financial support.

The Phase 1/2 trial (NCT03875313) will evaluate the safety and efficacy of the combination of telaglenastat plus talazoparib in patients with locally advanced/metastatic RCC, TNBC and CRC that are refractory or intolerant to standard therapies. The trial will evaluate the potential of telaglenastat to sensitize tumors to talazoparib in patients regardless of mutations in the BRCA gene.

Telaglenastat is an investigational, novel glutaminase inhibitor specifically designed to block glutamine consumption in tumor cells. Tumors commonly exhibit metabolic alterations that increase their dependence on glutamine. In preclinical studies, telaglenastat produced synergistic antitumor effects when used in combination with standard-of-care therapies.

On March 26, 2019 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next generation programmed T cell therapies for the treatment of cancer, reported to present insights into the science behind tumor defense mechanisms and the company’s novel programmed T cell therapy programs in development utilizing targeted, modular approaches designed to address these mechanisms at its inaugural R&D Day, in New York (Press release, Autolus, MAR 26, 2019, View Source [SID1234534687]). In addition, the company plans to provide an update on its AUTO3 program in pediatric acute lymphocytic leukemia (pALL).

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AUTO3 is the first dual-targeting CD19 and CD22 programmed T cell therapy in development for both pALL and relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Updated data from the ongoing AMELIA Phase 1/2 study in pALL demonstrates that 6 out of 6 (100%) patients treated at the highest dose (³3 x106/kg) achieved minimal residual disease (MRD) negative complete responses (CR). Ongoing MRD negative CR remissions were noted in 4 out of 6 (67%) patients, with duration of up to 10 months as of February 2019, the date of latest data follow-up. There have been no reported CD19 or CD22 negative relapses in CAR T naïve patients. Data also showed that AUTO3 continues to be generally well tolerated with no ³ Grade 3 CRS, no ICU admission, and no pressors or critical care support for CRS required. The Phase 2 portion of the study is expected to start in the second half of 2019. For more information about this trial and the inclusion criteria, visit www.ClinicalTrials.gov (NCT03289455).

"We are pleased to be hosting our inaugural R&D day, providing a unique opportunity to present an in-depth overview of our differentiated technology, multiple programs, market opportunities and the significant pipeline progress we have achieved, to date," stated Dr. Christian Itin, chairman and chief executive officer of Autolus. "We expect to report data on all of our active clinical programs at key medical conferences during 2019. Additionally, over the coming months, we expect to move two programs into registrational trials and to progress our next generation programs toward the clinic."

Today’s R&D program will include the following presentations:

Dr. Christian Itin, Chairman and Chief Executive Officer of Autolus – Welcome and Overview

Dr. Samir N. Khleif, Director of the Loop Immuno-Oncology Lab and Biomedical Scholar and Professor of Oncology, Georgetown University Medical Center – Immunotherapy, A Combinatorial Approach for Success

Dr. Muhammad Al-Hajj, Senior Vice President, Translational Sciences of Autolus – Translational Aspects of Tumor Heterogeneity

Dr. Martin Pule, Chief Scientific Officer and Founder of Autolus and Clinical Senior Lecturer at University College London Cancer Institute – Tackling Solid Tumors: A Modular Approach to T Cell Programming

Dr. Vijay Peddareddigari, Chief Medical Officer of Autolus – Clinical Update: Current and Next Generation Programs

LOGO

A live video webcast of the event will be available beginning at 8:00 am ET today on the Events section of Autolus’ website: View Source An archived replay will be available on the website for one year.

About AUTO3

AUTO3 is a programmed T cell therapy containing two independent chimeric antigen receptors targeting CD19 and CD22 that have each been independently optimized for single target activity. By simultaneously targeting two B cell antigens, AUTO3 is designed to minimize relapse due to single antigen loss in patients with B cell malignancies. AUTO3 is currently being tested in two clinical studies, AMELIA and ALEXANDER.

AMELIA is a single-arm, open label, multi-center Phase 1/2 clinical trial of AUTO3 in patients up to 24 years of age with high-risk relapsed or refractory B-lineage. The trial is also enrolling patients who previously received CD19 or CD22 targeting therapies including other CAR T cell therapy. The purpose of this study is to test the safety and efficacy, including the complete remission rate or minimal residual disease (MRD) negative response, of AUTO3. Autolus expects to enroll up to 54 patients in this trial.

ALEXANDER is a single-arm, open label, multi-center Phase 1/2 clinical trial of AUTO3 in patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL). The purpose of this study is to test the safety and efficacy, including the overall response rate as per Lugano criteria, of AUTO3 followed by limited duration of consolidation with anti-PD1 antibody. Autolus expects to enroll up to 120 patients in this trial.

For more information about these trials and the inclusion criteria, visit www.ClinicalTrials.gov.