- Results support the potential for combination of erymethionase with checkpoint inhibition
Erymethionase, methionine-gamma-lyase (MGL) encapsulated into red blood cells, is being developed as a novel antitumor therapy targeting cancer cells’ altered amino acid metabolism. MGL degrades L-methionine, an amino acid nutrient needed for tumor growth and metastasis. This enzyme is characterized by a limited half-life and its dependence on pyridoxal 5’-phosphate, the biologically active form of vitamin B6, as a co-factor. When coupled with oral vitamin B6 administration, erymethionase has demonstrated increased MGL half-life versus the free form of MGL, prolonged plasma methionine depletion and has shown significant tumor growth regression in mouse models of glioblastoma and gastric adenocarcinoma.12
The results presented today at the AACR conference highlight the potential for the combination of erymethionase with immune checkpoint inhibition. Along with in vitro data demonstrating that MGL upregulated the expression of PD-L1 on triple negative breast cancer cells, the combination of erymethionase and an anti-PD-1 monoclonal antibody demonstrated synergistic effect in a murine EMT6 syngeneic model of triple negative breast cancer. As compared to single agent therapy alone, tumor growth inhibition of 57% and a 52% increase in survival were observed.
The analysis of erymethionase-treated tumors revealed significant metabolic changes, providing initial mechanistic insight on how erymethionase sensitizes the tumor to anti PD-1 immunotherapy. Additionally, in vitro experiments demonstrating increased stimulation of immune cells with erymethionase also suggest that other immune checkpoint inhibitors, such as anti-CTLA-4 monoclonal antibodies, could be good candidates for further combination studies.
“In addition to the previously demonstrated potential of erymethionase as a monotherapy, these new findings may open up new therapeutic concepts linking immune checkpoint blockade to methionine metabolism,” stated Dr.
About ERYTECH: www.erytech.com
ERYTECH is a clinical-stage biopharmaceutical company developing innovative red blood cell-based therapeutics for cancer and orphan diseases. Leveraging its proprietary ERYCAPS platform, a novel technology to encapsulate drug substances inside red blood cells, ERYTECH is developing a pipeline of product candidates to address markets with high unmet medical needs.
ERYTECH’s primary focus is on the development of product candidates that target the altered metabolism of cancer cells by depriving them of amino acids necessary for their growth and survival. The Company’s lead product candidate, eryaspase, which consists of L-asparaginase encapsulated inside donor-derived red blood cells, targets the cancer cell’s altered asparagine and glutamine metabolism. Eryaspase is in Phase 3 clinical development for the treatment of second-line pancreatic cancer and in preparations to enter Phase 2 clinical development for the treatment of triple-negative breast cancer. ERYTECH’s next product candidate erymethionase, which consists of methionine-gamma-lyase encapsulated in red blood cells to target methionine-dependent cancers, has demonstrated promising preclinical results and is in preparations to enter Phase 1 clinical development.
ERYTECH is also exploring the use of its ERYCAPS platform for developing cancer immunotherapies (ERYMMUNE) and enzyme therapies (ERYZYME).
ERYTECH produces product candidates at its GMP-approved manufacturing site in Lyon,
ERYTECH is listed on the Nasdaq Global Select Market in the United States (ticker: ERYP) and on the Euronext regulated market in Paris (ISIN code: FR0011471135, ticker: ERYP). ERYTECH is part of the CAC Healthcare, CAC Pharma & Bio, CAC Mid & Small, CAC All Tradable, EnterNext PEA-PME 150 and Next Biotech indexes.
CFO & COO
Mathilde Bohin / Louis-Victor Delouvrier
+33 4 78 74 44 38
+33 1 44 71 94 94
This press release contains forward-looking statements, forecasts and estimates with respect to the clinical results from and the development plans of eryaspase, business and regulatory strategy, expansion of manufacturing capacity 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. All statements contained in this press release other than statements of historical facts are forward-looking statements, including, without limitation, statements regarding the potential of ERYTECH’s product pipeline, its clinical development and regulatory plans for eryaspase, the timing of ERYTECH’s clinical studies and trials and announcements of data from those studies and trials, and the contents and timing of decisions by the
1Cancer Medicine 2017; 6(6): 1437-1452
2Cancer Res 2017;77(13 Suppl): Abstract 2134
Source: Erytech Pharma S.A.