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Syros Presents New Preclinical Data on SY-1365 and SY-5609 at AACR Annual Meeting

Presentations Highlight Syros’ Leadership in Selective CDK7
Inhibition as Potentially Transformative Targeted Approach for
Difficult-to-Treat Cancers

Alterations in RB Pathway Predictive of Response to SY-1365 in
Ovarian Cancer Models,
Supporting Further Evaluation as Potential
Biomarker

Selectivity, Potency and Anti-Tumor Activity of SY-5609, an Oral CDK7
Inhibitor, Supports Advancement into IND-Enabling Studies

CAMBRIDGE, Mass.–(BUSINESS WIRE)–Syros Pharmaceuticals (NASDAQ: SYRS), a leader in the development of
medicines that control the expression of genes, today presented new
preclinical data across its franchise of selective cyclin-dependent
kinase 7 (CDK7) inhibitors at the American Association for Cancer
Research (AACR) Annual Meeting in Atlanta. New data on SY-1365, a
first-in-class selective CDK7 inhibitor currently in a Phase 1 clinical
trial, suggest that RB pathway alterations are predictive of response in
preclinical models of high-grade ovarian cancer (HGOC) and support the
ongoing clinical investigation of SY-1365 in patient populations
enriched for RB pathway alterations. New preclinical data on SY-5609, a
selective oral CDK7 inhibitor, demonstrate broad anti-tumor activity in
preclinical models of triple-negative breast cancer (TNBC) and ovarian
cancer.

The new data on SY-1365 and SY-5609 further demonstrate our leadership
in selective CDK7 inhibition, which we believe represents a potentially
transformative targeted approach for many difficult-to-treat cancers,”
said Eric R. Olson, Ph.D., Syros’ Chief Scientific Officer. “The data
highlight our ability to discover highly selective small molecule
inhibitors of CDK7, a target that has been historically difficult to
drug selectively, as well as to identify potential patient selection
strategies to enable targeted and efficient clinical development. We
remain focused on executing on the ongoing Phase 1 trial evaluating
SY-1365 in select ovarian and breast cancer patient populations that we
believe are most likely to respond. Meanwhile, we also continue to
advance SY-5609, our highly selective and potent oral CDK7 inhibitor,
toward a Phase 1 study. Together, we believe SY-1365 and SY-5609 could
make for a powerful CDK7 franchise with the potential to provide a
profound benefit for patients.”

RB Alterations Predictive of Response to SY-1365 in Preclinical Models
Researchers
from Syros evaluated tumor growth inhibition in a panel of HGOC patient
derived xenograft (PDX) models, including both high-grade serous ovarian
cancer (HGSOC) and clear cell ovarian cancer, to determine whether RB
pathway alterations predict response to treatment with SY-1365. RB
pathway alterations are present in 67 percent of HGSOC patients,
according to The Cancer Genome Atlas analysis. In Syros’ study, RB
pathway alterations were prospectively defined per The Cancer Genome
Atlas criteria – including RB1 deletion or mutation, CDKN2A
downregulation or deletion, CCNE1 amplification, CCND1 amplification, or
CCND2 upregulation.

These data show that:

  • Ninety percent (9 of 10) of the PDX models with RB pathway alterations
    responded to treatment with SY-1365.
  • Forty percent (6 of 15) of the PDX models without prospectively
    defined RB alterations responded to treatment with SY-1365, suggesting
    the presence of other undetected RB pathway changes or alternative
    mechanisms, including transcriptional regulation, conferring
    sensitivity to SY-1365.

Overall, Syros believes these results support the ongoing development of
SY-1365 in patient populations, including HGSOC and CDK4/6-inhibitor
resistant hormone receptor-positive (HR+) breast cancer, that are
enriched for RB pathway alterations, as well as the evaluation of these
alterations as potential biomarkers of response to SY-1365.

Syros is currently conducting a Phase 1 clinical trial assessing the
safety and efficacy of SY-1365 as a single agent and in combination with
standard-of-care therapies in multiple ovarian and breast cancer patient
populations. The trial includes cohorts evaluating SY-1365 as a single
agent in patients with relapsed ovarian clear cell cancer; as a single
agent in HGSOC patients who have had three or more prior lines of
therapy; in combination with carboplatin in HGSOC patients who have had
one or more prior lines of therapy; in combination with fulvestrant in
HR+ breast cancer patients who are resistant to treatment with a CDK4/6
inhibitor; and as a single agent in patients with solid tumors
accessible for biopsy. Syros expects to report initial clinical data
from the dose expansion portion of the trial in the fourth quarter of
2019. Additional details about the trial can be found using the
identifier NCT03134638 at www.clinicaltrials.gov.

SY-5609 Demonstrates Selectivity, Potency and Anti-Tumor Activity
Preclinically

Researchers from Syros conducted a series of
preclinical studies to characterize the in vitro and in vivo
profile of SY-5609. The data show that SY-5609:

  • Demonstrated 13,000- to 49,000-fold greater selectivity for CDK7 over
    other CDK family members, including CDK2, CDK9 and CDK12.
  • Induced robust tumor growth inhibition effects and cell cycle arrest
    in TNBC and ovarian cancer cell lines at low nanomolar drug
    concentrations, with apoptosis demonstrated only in the TNBC and
    ovarian cancer models, but not in non-cancerous cells.
  • Significantly impacted tumor growth in vivo, with complete
    regressions observed with SY-5609 as a monotherapy in multiple TNBC
    and ovarian cancer cell line xenograft models at doses below the
    maximum tolerated dose.
  • Demonstrated substantial tumor growth inhibition in multiple TNBC and
    ovarian cancer PDX models, with minimum weight loss observed.
  • Led to decreases in CDK7 downstream protein markers, including MCL1,
    in treated tumor tissue, confirming CDK7 inhibition in vivo.

Syros is currently advancing SY-5609 through investigational new drug
application enabling studies, with a Phase 1 oncology trial expected to
begin in early 2020.

The posters presented at AACR are now available on the Publications and
Abstracts section of the Syros website at www.syros.com.

About Syros Pharmaceuticals
Syros is pioneering the
understanding of the non-coding regulatory region of the genome to
advance a new wave of medicines that control the expression of genes.
Syros has built a proprietary platform that is designed to
systematically and efficiently analyze this unexploited region of DNA 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 monogenic 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 SY-1365, a selective CDK7 inhibitor in a Phase 1
clinical trial focused on patients with ovarian and breast cancers.
Syros is also developing a deep preclinical and discovery pipeline,
including SY-5609, an oral CDK7 inhibitor, as well as programs in
immuno-oncology and sickle cell disease. 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 relevance of RB pathway alterations
to predict response to SY-1365 in clinical trials and the ability to
identify a biomarker of response to SY-1365; the importance of CDK7
inhibition to address difficult-to-treat cancers and Syros’ ability to
develop a powerful CDK7 franchise; Syros’ ability to advance its
clinical-stage programs, including the timing and quantity of clinical
data to be reported from the expansion phase of the ongoing Phase 1
clinical trial of SY-1365; the ability to complete IND-enabling
preclinical studies and begin clinical development of SY-5609; and the
benefits of Syros’ gene control platform and product development
pipeline. The words ‘‘anticipate,’’ ‘‘believe,’’ ‘‘continue,’’
‘‘could,’’ ‘‘estimate,’’ ‘‘expect,’’ “hope,” ‘‘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-1365, under the timelines it projects in current
and future clinical trials; demonstrate in any current and future
clinical trials the requisite safety, efficacy and combinability of its
drug candidates; successfully progress SY-5609 through IND-enabling
preclinical and toxicology studies; replicate scientific and
non-clinical data in clinical trials; 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, including its ability to perform under
the collaboration agreement with Incyte; 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, 2018, 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 Contact:
Naomi Aoki
Syros Pharmaceuticals
617-283-4298
[email protected]
Investor
Contact:

Hannah Deresiewicz
Stern Investor Relations, Inc.
212-362-1200
[email protected]

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