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ERYTECH ANNOUNCES LAUNCH OF INVESTIGATOR-INITIATED PHASE 2 STUDY OF ERYASPASE (GRASPA®) FOR ALL

On April 4, 2017 ERYTECH Pharma (Paris:ERYP) (ADR:EYRYY) a French clinical-stage biopharmaceutical company developing innovative therapies by encapsulating therapeutic drug substances inside red blood cells, reported the launch of an investigator-initiated study to evaluate eryaspase, also known by the trade name GRASPA, in patients with acute lymphoblastic leukemia (ALL) (Press release, ERYtech Pharma, APR 4, 2017, View Source [SID1234518478]). The study will take place in seven Nordic countries and be conducted in collaboration with the Nordic Society of Pediatric Hematology and Oncology (NOPHO).

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The single arm, multi-center, multi-national Phase 2 study is expected to enroll approximately 30 patients at 23 sites across seven Nordic and Baltic countries: Denmark, Finland, Norway, Sweden, Iceland, Lithuania and Estonia. The main objectives of the study are to evaluate the biological (pharmacokinetic and pharmacodynamic) activity, safety, and immunogenicity profile of eryaspase in combination with the NOPHO ALL 2008 multi-agent chemotherapy protocol administered as second-intention treatment for children or adult ALL patients (1 to 45 years old) who experience hypersensitivity reactions to PEG-asparaginase or silent inactivation. The study is expected to start in April 2017 and continue for approximately 2 years.

Dr. Birgitte Klug Albertsen, Principal Investigator of the trial, commented, "Depending on the asparaginase preparation, hypersensitivity reactions can occur at frequencies between 13% and 30% of children and adults with ALL, making the therapy ineffective. Eryaspase, or L-asparaginase encapsulated in red blood cells, may be able to limit these reactions and maintain treatment effectiveness. We look forward to evaluating this combination therapy to determine its clinical benefits for both pediatric and adult patients with hypersensitivity reactions to the PEG-asparaginase chemotherapy."

Dr. Iman El-Hariry, Chief Medical Officer of Erytech Pharma, added, "Collaborating with NOPHO is an exciting opportunity for Erytech to evaluate eryaspase in this specific patient population, with the potential to demonstrate expanded application of our technology to treat blood cancers where drug resistance and hypersensitivity clinical reactions to first-line chemotherapies is common. This study aligns with our global strategy to develop the ERYCAPS technology with an increased tolerability and efficacy profile for patients who may respond to L-asparaginase when it is delivered through encapsulated red blood cells."

About ERYTECH: www.erytech.com

Founded in Lyon, France in 2004, ERYTECH is a clinical-stage biopharmaceutical company developing innovative therapies for rare forms of cancer and orphan diseases. Leveraging its proprietary ERYCAPS platform, which uses a novel technology to encapsulate therapeutic drug substances inside red blood cells, ERYTECH has developed a pipeline of product candidates targeting markets with high unmet medical needs. ERYTECH’s initial focus is on the treatment of blood cancers, including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), by depriving tumors of nutrients necessary for their survival. ERYTECH plans to pursue regulatory approvals for its lead product candidate, eryaspase, also known as ERY-ASP or under the trade name GRASPA, having achieved positive efficacy and safety results from its completed Phase 2/3 pivotal clinical trial in Europe in children and adults with relapsed or refractory ALL. ERYTECH also has an ongoing Phase 1 clinical trial of eryaspase in the United States in adults with newly diagnosed ALL, and a Phase 2b clinical trial in Europe in elderly patients with newly diagnosed AML, each in combination with chemotherapy. ERYTECH believes that eryaspase also has the potential as a treatment approach in solid tumors and is conducting a Phase 2 clinical trial in Europe in patients with metastatic pancreatic cancer.

Eryaspase consists of an enzyme, L-asparaginase, encapsulated inside donor-derived red blood cells. L-asparaginase depletes asparagine, a naturally occurring amino acid essential for the survival and proliferation of cancer cells, from circulating blood plasma. ERYTECH produces eryaspase at its own GMP-approved and operational manufacturing site in Lyon (France), and at a site for clinical production in Philadelphia (USA). ERYTECH has entered into licensing and distribution partnership agreements for eryaspase for ALL and AML in Europe with Orphan Europe (Recordati Group), and for ALL in Israel with TEVA, which will market the product under the GRASPA brand name. The European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) have granted orphan drug designations for eryaspase for the treatment of ALL, AML and pancreatic cancer.

In addition to eryaspase, ERYTECH is developing two other product candidates that focus on using encapsulated enzymes to induce tumor starvation. The company is leveraging the ERYCAPS platform for developing cancer immunotherapies (ERYMMUNE) and enzyme therapies beyond oncology (ERYZYME).

ERYTECH is listed on Euronext regulated market in Paris (ISIN code: FR0011471135, ticker: ERYP) and is part of the CAC Healthcare, CAC Pharma & Bio, CAC Mid & Small, CAC All Tradable, EnterNext PEA-PME 150 and Next Biotech indexes. ERYTECH is also listed in the U.S. under an ADR level 1 program (OTC, ticker EYRYY).

Forward-looking information

This press release contains forward-looking statements, forecasts and estimates with respect to the clinical development plans, business and regulatory strategy, and anticipated future performance of ERYTECH and of the market in which it operates. Certain of these statements, forecasts and estimates can be recognized by the use of words such as, without limitation, "believes", "anticipates", "expects", "intends", "plans", "seeks", "estimates", "may", "will" and "continue" and similar expressions. They include all matters that are not historical facts. Such statements, forecasts and estimates are based on various assumptions and assessments of known and unknown risks, uncertainties and other factors, which were deemed reasonable when made but may or may not prove to be correct. Actual events are difficult to predict and may depend upon factors that are beyond ERYTECH’s control. There can be no guarantees with respect to pipeline product candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. Therefore, actual results may turn out to be materially different from the anticipated future results, performance or achievements expressed or implied by such statements, forecasts and estimates. Documents filed by ERYTECH Pharma with the French Autorité des Marchés Financiers (www.amf-france.org), also available on ERYTECH’s website (www.erytech.com) describe such risks and uncertainties. Given these uncertainties, no representations are made as to the accuracy or fairness of such forward-looking statements, forecasts and estimates. Furthermore, forward-looking statements, forecasts and estimates only speak as of the date of this press release. Readers are cautioned not to place undue reliance on any of these forward-looking statements. ERYTECH disclaims any obligation to update any such forward-looking statement, forecast or estimates to reflect any change in ERYTECH’s expectations with regard thereto, or any change in events, conditions or circumstances on which any such statement, forecast or estimate is based, except to the extent required by law.

SYROS PRESENTS DATA AT AACR FURTHER SUPPORTING CLINICAL POTENTIAL OF SY-1425, ITS FIRST-IN-CLASS SELECTIVE RARΑ AGONIST, FOR GENOMICALLY DEFINED AML AND MDS PATIENTS

On April 4, 2017 Syros Pharmaceuticals (NASDAQ:SYRS), a biopharmaceutical company pioneering the discovery and development of medicines to control the expression of disease-driving genes, announced today that new preclinical data on SY-1425, its first-in-class selective retinoic acid receptor alpha (RARα) agonist currently in a Phase 2 clinical trial in genomically defined subsets of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), were presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Washington, D.C (Press release, Syros Pharmaceuticals, APR 4, 2017, View Source [SID1234518477]).

"Our clinical strategy with SY-1425 is to quickly and efficiently explore its potential as both a single agent and in combination for AML and MDS patients whose disease is driven by the abnormal expression of RARA pathway-associated genes, including RARA and IRF8," said Nancy Simonian, M.D., Chief Executive Officer of Syros. "The new data presented at AACR (Free AACR Whitepaper) provide the foundation for our rational combination strategy, supporting the expansion of our ongoing Phase 2 clinical trial to include a combination dosing arm with hypomethylating agent therapy, as well as the future clinical investigation of SY-1425 in combination with anti-CD38 therapies."

SY-1425 in Combination with Hypomethylating AML and MDS Therapies

Data generated and presented by Syros scientists show SY-1425 increases the anti-tumor activity of hypomethylating agents (HMAs), including azacitidine, a therapy used as a standard-of-care in AML and MDS, in in vitro and in vivo models of AML with high levels of RARA expression. HMAs prime the DNA for gene activation, thus enhancing SY-1425’s gene activation and differentiation properties. In patient-derived xenograft (PDX) models of AML with high RARA expression, SY-1425 in combination with azacitidine shows:

Greater clearance of tumor cells and duration of response, compared to either azacitidine or SY-1425 alone.
Reduction of tumor burden to less than 5 percent in bone marrow and other tissues.
Based on these data, Syros has expanded its ongoing Phase 2 clinical trial to include an arm to explore the safety and efficacy of SY-1425 in combination with azacitidine in newly diagnosed AML patients 60 years or older who are not suitable candidates for standard chemotherapy and who have been prospectively identified as positive for one of the Company’s two biomarkers. The treatment regimen for patients in the combination arm is consistent with the one identified in preclinical studies to maximize tumor suppression and tolerability, with seven days of azacitidine treatment followed by 21 days of SY-1425 treatment. In these preclinical studies, both agents were administered at full doses and no unexpected safety events were observed.

SY-1425 Sensitizes RARA-High AML Cells to Anti-CD38 Therapeutic Antibody

Data generated and presented by Syros scientists demonstrate that SY-1425 induces the cell surface protein CD38 in AML cells from patient samples with high levels of RARA expression. By inducing CD38, SY-1425 sensitizes the cancer cells to daratumumab, an anti-CD38 monoclonal antibody that flags CD38-positive tumor cells for immune cell-mediated killing. Daratumumab is approved to treat various multiple myeloma (MM) populations. Results from the in vitro studies show SY-1425:

Induces levels of CD38 expression in RARA-high AML cells comparable to those in MM cells that are known to be responsive to daratumumab; notably, AML cells do not normally express high levels of CD38.
Triggers robust activation of natural killer cells when combined with daratumumab in RARA-high AML cells.
Leads to potent immune cell-mediated tumor cell death in RARA-high AML cells when combined with daratumumab.
Based on these data, Syros believes SY-1425 in combination with a therapeutic anti-CD38 antibody represents a promising immunotherapy approach for defined subsets of AML and MDS patients and plans to pursue clinical development of the combination in patients identified using the Company’s biomarkers.

High IRF8 Expression Predicts Response to SY-1425 in Models of AML

Using its gene control platform, Syros identified a super-enhancer associated with the IRF8 gene in a subset of AML tumors that, like the RARA super-enhancer, is predictive of response to treatment with SY-1425. The IRF8 super-enhancer drives overexpression of the IRF8 gene, which codes for the IRF8 transcription factor. IRF8 works cooperatively with the RARα transcription factor to induce differentiation and reduce proliferation in AML cells. While the IRF8 and RARA super-enhancers as well as high IRF8 and RARA expression are correlated, a subset of AML patient tumors has high IRF8 expression in the absence of high RARA expression.

Data presented by Syros scientists show that cell-line models of AML with high expression of IRF8 are 1,000 times more sensitive to SY-1425 than AML models with low IRF8 expression. SY-1425 induced differentiation in AML cells with high IRF8 expression as well as in an ex vivo clinical sample from a patient positive for a biomarker for the IRF8 super-enhancer discovered by Syros.

Syros’ patient selection strategy for the ongoing Phase 2 clinical trial incorporates biomarkers for both the RARA and IRF8 super-enhancers. Syros estimates that about one-third of AML and MDS patients will have one or both biomarkers.

About the Phase 2 Clinical Trial of SY-1425

The Phase 2 clinical trial of SY-1425 is a biomarker-directed multi-center, open-label trial exploring safety and efficacy in relapsed or refractory AML and higher-risk MDS patients, newly diagnosed AML patients 60 years of age or older who are not suitable candidates for standard chemotherapy and lower-risk transfusion-dependent MDS patients. The trial also includes an arm to explore the safety and efficacy of SY-1425 in combination with azacitidine in newly diagnosed AML patients 60 years of age or older who are not suitable candidates for standard chemotherapy. All patients in the trial are prospectively selected using the Company’s proprietary biomarkers. The primary endpoint is overall response rate for AML and higher-risk MDS patients and red blood cell transfusion-independence rate for lower-risk MDS patients. Other endpoints include assessment of pharmacodynamic markers, duration of response, safety and tolerability, and overall and progression-free survival. Additional details about the trial can be found using the identifier NCT02807558 at www.clinicaltrials.gov. Syros is on track to report initial clinical data on SY-1425 in fall 2017.

About Syros Pharmaceuticals

NATIVIS ENTERS INTO EXCLUSIVE LICENSING AGREEMENT FOR GLIOBLASTOMA MULTIFORME IN JAPAN

On April 4, 2017 Nativis, Inc. (Nativis), a clinical-stage life science bio-electronic company developing non-invasive, safe and highly effective treatments for cancers and other serious diseases, reported that the company has entered into an exclusive licensing agreement for the development and commercialization of Nativis’ proprietary ultra-low Radio Frequency Energy (ulRFE) technology for the potential treatment of Glioblastoma Multiforme (GBM) in the Japanese market, with Teijin Limited (Teijin), a comprehensive Japanese company expanding businesses in high-performance materials, pharmaceuticals, home healthcare, product converting and information technology (Press release, Nativis, APR 4, 2017, View Source [SID1234518476]).

Under the terms of the agreement, Teijin will receive an exclusive license to the Nativis Voyager System for the indication of GBM in Japan. Nativis will receive an undisclosed upfront payment, payments based on the achievement of specific regulatory and commercial milestones, and royalties on the sales of the product in Japan. Teijin will sublicense its rights under the agreement to Teijin Pharma Limited (Teijin Pharma), Teijin’s wholly-owned subsidiary and the core company of Teijin Group’s healthcare business, under which Teijin Pharma will develop and commercialize the licensed technology in Japan.

Nativis and Teijin also anticipate expansion of the scope of the alliance and will continue discussions for potential licensing opportunities of the Nativis ulRFE technology for other indications in Japan.

"We are very pleased to enter into this exclusive licensing agreement with Teijin for GBM; the company has a strong track record of successfully commercializing pharmaceuticals and medical devices in Japan. We believe that this partnership further validates our technology, while their investment in Nativis reinforces our belief in the broader potential of the Voyager platform. With their support, we look forward to further developing and refining the Voyager System for GBM, as well as additional indications in the future," commented Chris Rivera, President and Chief Executive Officer of Nativis. "This agreement also brings us one step closer to reaching our goal of becoming cash flow positive through strategic partnerships and licenses, and we are excited to work closely with Teijin to bring the Voyager System to market in Japan."O

CBT Pharmaceuticals Presents Data Demonstrating Anti-Tumor Activity of its Highly Specific c-MET Inhibitor, Bozitinib (CBT-101), at AACR Annual Meeting 2017

On April 4, 2017 CBT Pharmaceuticals, Inc. (CBT), a life sciences company focused on developing innovative oncology therapeutics, presented preclinical data on CBT-101 (bozitinib, PLB-1001, CBI-3103), a highly specific small molecule inhibitor of c-MET receptor tyrosine kinase, demonstrating its selectivity, safety, and efficacy in suppressing tumor growth in lung, gastric, hepatic and pancreatic human primary tumor models (Press release, CBT Pharmaceuticals, APR 4, 2017, View Source [SID1234518475]). The data were presented in a poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (AACR) (Free AACR Whitepaper) being held from April 1 – 5, 2017 in Washington, D.C.

Presentation Highlights:

CBT-101 inhibited c-MET activation in a range of human primary cancer cell lines.
CBT-101 inhibited in vivo dephosphorylation of c-MET in a dose-dependent manner in a human gastric cancer model.
CBT-101 demonstrated improved tumor growth inhibition as compared to other selective c-MET agents in lung, gastric, hepatic, and pancreatic cancer models.
"These preclinical data support our commitment to advancing the clinical development of bozitinib as a targeted therapy for c-MET dysregulated tumors," said Sanjeev Redkar, Ph.D., President and Chief Executive Officer of CBT Pharmaceuticals. "Based on these promising findings, we plan to submit an Investigational New Drug Application soon and initiate a Phase 1 dose escalation and dose and disease expansion study in 2017."

Bozitinib (CBT-101)

Bozitinib is an orally available tyrosine kinase inhibitor that is expected to potently target tumors in patients with c-MET driver alterations (amplification and mutation) that occur in varying percentages across a variety of tumor types, including, but not limited to, breast, colorectal, gastric, gliomas, head and neck, hepatocellular, lung, ovarian as well as hematologic malignancies. MET is a receptor tyrosine kinase located on the cell surface and is activated by the binding of its ligand, hepatocyte growth factor (HGF). MET activates a variety of signaling pathways within the cell, and in normal circumstances, is involved in embryonic development and wound healing. However, in cancer cells, MET can be aberrantly active and cause abnormal signaling, which leads to tumor growth, angiogenesis, and metastasis. CBT-101 has demonstrated high-affinity to MET irrespective of hepatocye growth factor (HGF) dependency and excellent activity in preclinical models of human cancer. CBT-101 was developed by Crown Bioscience. Beijing Pearl Biotechnology owns development and commercialization rights in People’s Republic of China. CBT retains rest of the world (ROW) rights. An investigational new drug application has been approved by the China Food and Drug Administration (CFDA), and two Phase 1 trials are ongoing in China – non-small cell lung cancer (NSCLC) (NCT02896231) and high grade gliomas with PTPRZ1-MET fusion gene (NCT02978261).

Intensity Therapeutics reports that INT230-6 Induces Protective T-Cell Immunity in preclinical models

On April 4, 2017 Intensity Therapeutics, Inc., a privately held biotechnology company developing proprietary immune cell-activating cancer treatments, reported that tumor regression and immune activation data generated by the Company’s lead drug, INT230-6, will be presented in a poster session at the American Academy of Cancer Research (AACR) (Free AACR Whitepaper) meeting on April 5, 2017 (Press release, Intensity Therapeutics, APR 4, 2017, View Source [SID1234518474]). The research being presented indicates that INT230-6 results in complete response of tumors in rodent models, induces protective T cell immunity and is synergistic with checkpoint inhibitors. Dr. Anja Bloom from the Vaccine Branch of the National Cancer Institute (NCI) and Lewis H. Bender, CEO of Intensity Therapeutics will present the poster presentation.

tumor regression & immune activation data for INT230-6 being presented at #AACR2017 on 4/5 http://bit.ly/2nHyrOX
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A series of preclinical studies conducted in collaboration with scientists from the Vaccine Branch at the NCI showed INT230-6 treatment leads to complete responses in rodents and a durable response. The subsequent protective effect against re-inoculation decreased when CD4- and CD8-positive T cells were depleted prior to treatment or re-challenge. The data indicate that the observed complete response and durable, vaccine-like anti-cancer effect of INT230-6 is immune mediated.

Intensity’s Chief Executive Officer Lewis H. Bender explained, "The direct killing action and immune response data generated in rodent models from our lead drug INT230-6 are impressive. We hope these animal results translate into an equally potent response in our clinical study, IT-01 for INT230-6, which is now recruiting patients in both the U.S. and Canada. Should the protective T cell immunity occur in humans, then INT230-6 could represent an important advance in the treatment of certain solid tumor cancers, potentially providing oncologists with a less toxic means to destroy visible tumors, eliminate metastases and prevent disease recurrence."

Presentation Details

Poster Title: Tumor cell death caused by INT230-6 induces protective T cell immunity
Session Category: Clinical Research
Session Title: Innate Immunity to Generate Adaptive Immunity
Session Date and Time: Wednesday Apr 5, 2017 8:00 AM – 12:00 PM
Location: Convention Center, Halls A-C, Poster Section 28
Poster Board Number: 14
Permanent Abstract Number: 5660

About INT230-6

INT230-6 is a novel, anti-cancer drug product able to disperse through tumors and diffuse into cancer cells. The product was identified from Intensity’s DfuseRxSM platform technology and is currently in a clinical trial; IT-01. In preclinical studies conducted in by Intensity Therapeutics alone and in collaboration with the Vaccine Branch of the National Cancer Institute (NCI), INT230-6 administration was shown to increase recruitment of dendritic cells to the tumor micro-environment followed by T-cell activation. Treatment with INT230-6 in in vivo models of severe cancer completely cleared large tumors in animal models and generate substantial improvement in overall survival compared to standard therapies. Further, INT230-6 provided complete responders in these preclinical studies with long-term, durable protection from multiple re-inoculations of the cancer, demonstrating the potential to eliminate metastases and prevent disease recurrence.

About Study IT-01

IT-01 is entitled A Phase 1/2 Safety Study of Intratumorally Administered INT230-6 in Adult Subjects with Advanced Refractory Cancers. The trial aims to enroll patients with different types of advanced solid tumor malignancies in a multicycle dosing regimen. IT-01 plans to include a cohort combining INT230-6 with an anti-PD-1 antibody. Currently the study is recruiting in the U.S. at the University of Southern California (USC) and in Canada at the University Health Network (UHN) in Toronto. The principal investigator at USC is Dr. Anthony El-Khoueiry; the principal investigator at UHN is Dr. Lillian Siu. The study’s primary objective is to assess the safety and tolerability of multiple intratumoral doses of INT230-6. Secondary assessments are to understand preliminary efficacy of INT230-6. The study will characterize the pharmacokinetic profile of multiple doses of INT230-6 components. Exploratory analysis will characterize patient outcome, as well as evaluate various tumor and anti-tumor immune response biomarkers that may correlate with response. Data will be used to assess the progression free and overall survival in subjects receiving INT230-6. Further information can be found at www.clinicaltrials.gov (NCT#03058289).

About the Vaccine Branch of the NCI

The Molecular Immunogenetics & Vaccine Research Section (Berzofsky lab) within the Vaccine Branch studies, in animals and clinical trials, the immunology of antigen-specific T cell activation and regulation, and translation to strategies for design of vaccines for HIV, cancer, and viruses that cause cancer. Approaches include use of synergistic combinations of cytokines and TLR ligands in vaccines, approaches to increase CTL avidity, analysis of a new NKT cell immunoregulatory axis and regulatory circuit that inhibits tumor immunity and vaccine-induced immune responses against cancer and its interactions with other regulatory mechanisms and blockade of these to improve vaccine efficacy, strategies to induce mucosal immunity and mechanisms of mucosal trafficking and homing, epitope enhancement by sequence modification, and development of new cancer vaccines as well as AIDS vaccine strategies. Several basic discoveries are currently being translated into clinical trials.