Syros Presents Discovery of Key Genes Controlling the Autoimmune Response in Lupus in Late-Breaking Oral Presentation at FOCIS Meeting

Analysis of Regulatory Genome of T Cells from Lupus Patients Reveals
Disease-Driving Alterations in Transcriptional Circuitry

Findings Underscore the Promise of Syros’ Gene Control Platform to
Identify Novel Drug Targets and Therapeutic Approaches for Autoimmune
Diseases

CAMBRIDGE, Mass.–(BUSINESS WIRE)–Syros Pharmaceuticals (NASDAQ:SYRS), a biopharmaceutical company
pioneering the discovery and development of medicines to control the
expression of disease-driving genes, today announced that the Company
has discovered alterations in regulatory regions of the genome in T
cells from patients with systemic lupus erythematosus (SLE), revealing
genes critical for activating T cells and driving disease. These
findings provide important biological insights into the autoimmune
response in lupus that could lead to the identification of novel drug
targets and therapeutic approaches to treat SLE. The research was
highlighted in a late-breaking oral presentation at the 17th
Annual Meeting of the Federation of Clinical Immunology Societies
(FOCIS).

“Syros’ gene control platform provides a unique lens for understanding
the abnormal immune response in lupus that causes the body to attack
itself and for developing medicines to control the expression of genes
to dampen that auto-immune response,” said Eric Olson, Ph.D., Syros’
Chief Scientific Officer. “Regulatory regions of the genome are known to
play a key role in the activation of T cells, but these findings are the
first to elucidate disease-driving alterations in those regions in T
cells from lupus patients. We believe our focus on the regulatory genome
of immune cells has the potential to lead to better treatments for lupus
patients, as well as the ability to identify subsets of patients most
likely to respond to specific therapeutic approaches.”

Using its proprietary gene control platform to analyze and compare the
regulatory genomes of T cells from lupus patients and healthy donors,
Syros scientists identified changes in highly specialized non-coding
regulatory regions of DNA, known as super-enhancers, in naive, memory,
and regulatory T cells. Because super-enhancers bring together large
amounts of transcription factors and other regulatory proteins to drive
the expression of the set of genes most critical to a given cell, their
analysis sheds light on the complex transcriptional regulatory circuits
that control the expression of critical genes and determine cell
function. The data showed that:

  • Super-enhancers found in T cells from healthy donors are associated
    with genes known to be important in determining cell state and
    function in all T cell types, including naïve, memory and regulatory T
    cells, providing strong validation for this novel genomics-based
    approach by recapitulating known biology.
  • Super-enhancer profiles of all T cell types are markedly different in
    SLE patients than in healthy donors, with naïve T cells in SLE
    displaying changes in their enhancer profiles that point to critical
    transcription factor networks driving disease.
  • Genes regulated by activation of the SYK kinase and IRF4 transcription
    factor are significantly enriched in SLE naïve and memory T cells,
    suggesting they are key drivers of T cell activation in SLE and a core
    part of the transcriptional regulatory circuitry driving the disease.
    Notably, the activation of IRF4-driven transcriptional cirtuitry in
    SLE T cells points to common mechanisms driving the activation of both
    T and B cells in SLE.
  • Super-enhancer profiles of memory T cells, especially in SLE, display
    considerable heterogeneity. This heterogeneity may provide an
    opportunity for the development of patient stratification biomarkers
    to better identify patient subsets and essential drivers of disease
    specific to these subsets.

As part of its research program in lupus, Syros has analyzed regulatory
regions of the genome in both T cells and B cells from SLE patients to
identify key genes controlling the activation of these immune cells in
SLE with the objective of developing medicines that selectively inhibit
disease-driving cells, dampening the auto-immune response. Syros has
identified multiple potential drug targets in human B cells and T cells
that it is investigating in preclinical studies, including a drug target
that when inhibited by a small molecule inhibitor in an in vivo
study selectively blocked the activation of antibody-producing plasma
cells.

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 in a Phase 1 clinical trial for patients with advanced solid
tumors, including transcriptionally dependent cancers such as triple
negative breast, small cell lung and ovarian 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 the benefits of Syros’
gene control platform, including its ability to identify novel drug
targets and therapeutic approaches for SLE and to identify patient
subsets more likely to respond to therapy. 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 under the timelines it projects in current and future
studies; replicate scientific and non-clinical data; obtain and maintain
patent protection for its drug candidates and the freedom to operate
under third party intellectual property; 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’ Quarterly Report on Form 10-Q for the quarter
ended March 31, 2017, 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.

Contacts

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