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.

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]).

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"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