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
– New Preclinical Data Demonstrate Synergistic Anti-Tumor Activity of SY-1425 with Standard-of-Care AML and
MDS Therapies, Providing Evidence for Expansion of Ongoing Phase 2 Clinical Trial to Include Combination with Azacitidine –
– New Preclinical Data Show SY-1425 Sensitizes AML Cells with High RARA Expression to Approved Multiple
Myeloma Drug by Inducing Expression of CD38, Providing Rationale for Clinical Investigation of SY-1425 in Combination with
Anti-CD38 Therapies –
– Exploratory Biomarker for High IRF8 Expression Revealed as One of Two Biomarkers for Patient Selection in
Ongoing Phase 2 Clinical Trial –
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) Annual Meeting in Washington, D.C.
“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 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
Syros Pharmaceuticals is pioneering the understanding of the non-coding region of the genome to advance a new wave of medicines
that control expression of disease-driving genes. Syros has built a proprietary platform that is designed to systematically and
efficiently analyze this unexploited region of DNA in human disease tissue to identify and drug novel targets linked to genomically
defined patient populations. Because gene expression is fundamental to the function of all cells, Syros’ gene control platform
has broad potential to create medicines that achieve profound and durable benefit across a range of diseases. Syros is
currently focused on cancer and immune-mediated diseases and is advancing a growing pipeline of gene control medicines. Syros’ lead
drug candidates are SY-1425, a selective RARα agonist in a Phase 2 clinical trial for genomically defined subsets of patients with
acute myeloid leukemia and myelodysplastic syndrome, and SY-1365, a selective CDK7 inhibitor with potential in a range of solid
tumors and blood cancers. Led by a team with deep experience in drug discovery, development and commercialization, Syros is located
in Cambridge, Mass.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of
1995, including without limitation statements regarding: presentation of initial clinical data for SY-1425; initiation of
combination dosing of SY-1425, including the planned combination of SY-1425 with daratumumab; the potential of SY-1425 as an
immunotherapy approach when combined with an anti-CD38 antibody; and the percentage of AML and MDS patients with the RARA or
IRF8 biomarkers. The words ‘‘anticipate,’’ ‘‘believe,’’ ‘‘continue,’’ ‘‘could,’’ ‘‘estimate,’’ ‘‘expect,’’ ‘‘intend,’’
‘‘may,’’ ‘‘plan,’’ ‘‘potential,’’ ‘‘predict,’’ ‘‘project,’’ ‘‘target,’’ ‘‘should,’’ ‘‘would,’’ and similar expressions are intended
to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results
or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a
result of various important factors, including: Syros’ ability to: advance the development of its programs, including SY-1425 under
the timelines it projects in current and future clinical trials; obtain and maintain patent protection for its drug candidates and
the freedom to operate under third party intellectual property; demonstrate in any current and future clinical trials the requisite
safety, efficacy and combinability of its drug candidates; replicate scientific and non-clinical data in clinical trials;
successfully develop a companion diagnostic test to identify patients with biomarkers associated with the RARA
super-enhancer; obtain and maintain necessary regulatory approvals; identify, enter into and maintain collaboration agreements with
third parties; manage competition; manage expenses; raise the substantial additional capital needed to achieve its business
objectives; attract and retain qualified personnel; and successfully execute on its business strategies; risks described under the
caption “Risk Factors” in Syros’ Annual Report on Form 10-K for the year ended December 31, 2016, which is on file with the
Securities and Exchange Commission; and risks described in other filings that Syros makes with the Securities and Exchange
Commission in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and
Syros expressly disclaims any obligation to update any forward-looking statements, whether because of new information, future
events or otherwise.
![](http://cts.businesswire.com/ct/CT?id=bwnews&sty=20170404005530r1&sid=mstr2&distro=nx&lang=en)
Media:
Syros Pharmaceuticals
Naomi Aoki, 617-283-4298
naoki@syros.com
or
Investors:
Stern Investor Relations, Inc.
Hannah Deresiewicz, 212-362-1200
hannahd@sternir.com
View source version on businesswire.com: http://www.businesswire.com/news/home/20170404005530/en/