On April 18, 2016 Syros Pharmaceuticals reported that SY-1425, a potent and selective retinoic acid receptor alpha (RARα) agonist, was observed to inhibit the growth of cancer cells and prolong survival in in vivo models of acute myeloid leukemia (AML) with a novel RARA biomarker discovered by the Company (Press release, Syros Pharmaceuticals, APR 18, 2016, View Source [SID:1234511012]). The biomarker was found in approximately 25 percent of AML and myelodysplastic syndrome (MDS) patient tissue samples. These data were presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in New Orleans. Schedule your 30 min Free 1stOncology Demo! "SY-1425 represents a promising therapeutic option for novel genomically defined subsets of AML and MDS patients," said Nancy Simonian, MD, Chief Executive Officer of Syros. "Based on our preclinical data, which show a strong link between our biomarker and response to treatment with SY-1425, we are committed to rapidly advancing this first-inclass therapy for these currently underserved patients. Positive results from a Phase 2 clinical study would not only be beneficial to patients but also validate our pioneering approach of analyzing the non-coding region of DNA to advance the field of genomics-based medicine."
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The data presented at AACR (Free AACR Whitepaper) shows that the RARA biomarker discovered by Syros is predictive of response to treatment with SY-1425 in AML cell lines and patient-derived xenograft (PDX) models of AML. Treatment with SY-1425 was observed to inhibit cancer growth and prolong survival in PDX models of AML with the RARA biomarker but not in models of AML without the biomarker. Highlights of the data include:
Greatly reduced tumor burden in the blood, bone marrow and spleen in PDX mouse models with the RARA biomarker treated with SY-1425 compared to untreated mice; by contrast, no effect was seen in PDX models of AML without the biomarker.
Prolonged survival with 100 percent of mice with the RARA biomarker treated with SY-1425 alive at the end of the 35-day study; by contrast, none of the untreated mice survived beyond 25 days; also, by contrast, no survival benefit was seen in PDX models of AML without the biomarker.
Significant survival benefit in mice treated with SY-1425 compared to mice treated with ATRA, a pan-agonist of RAR, RAR and RARA, in a PDX model with the RARA biomarker.
Using its gene control platform, Syros identified a specialized regulatory region of noncoding DNA known as a super-enhancer that is associated with the RARA gene in subsets of AML and MDS patients. The super-enhancer is believed to lock cells in an immature, proliferative state. Treatment with SY-1425 in cancer cells with the RARA super-enhancer appears to promote differentiation of these cells. Syros in-licensed SY-1425, which is approved in Japan as tamibarotene to treat acute promyelocytic leukemia, to develop and commercialize SY-1425 in North America and Europe for all cancers.
Syros plans to file an Investigational New Drug (IND) application with the U.S. Food and Drug Administration and initiate a Phase 2 clinical trial of SY-1425 in mid-2016 in subsets of AML and MDS patients with the RARA biomarker. The Company continues to research the role of the RARA super-enhancer in other cancers and plans to pursue additional indications upon achieving proof-of-concept in AML and MDS.