Syros Presents PK & PD Data at ESMO for SY-1425, Its First-in-Class Selective RARα Agonist, in Genomically Defined AML & MDS...
September 11 2017 - 7:01AM
Business Wire
Data from Ongoing Phase 2 Clinical Trial Shows
Favorable PK and Evidence of RARα Target Engagement in Patients
with Proprietary RARA or IRF8 Biomarkers
Company Expects to Present Initial Phase 2
Clinical Data for SY-1425 in Fourth Quarter of 2017
Company Also Details SY-1365 Phase 1 Clinical
Trial Design
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
pharmacokinetic (PK) and pharmacodynamic (PD) data from the ongoing
Phase 2 clinical trial of SY-1425, its first-in-class selective
retinoic acid receptor alpha (RARα) agonist, in genomically defined
subsets of patients with acute myeloid leukemia (AML) and
myelodysplastic syndrome (MDS), were presented at the European
Society of Medical Oncology (ESMO) 2017 Congress in Madrid. Syros
also presented the design of its ongoing Phase 1 clinical trial for
SY-1365, a first-in-class selective cyclin-dependent kinase 7
(CDK7) inhibitor, in patients with advanced solid tumors.
“The PK and PD data we have seen to date from the ongoing Phase
2 clinical trial show that the dosing regimen of SY-1425 is
achieving the intended drug exposure and eliciting a robust PD
response with evidence of RARα target engagement,” said David A.
Roth, M.D., Chief Medical Officer of Syros. “Importantly, SY-1425
showed favorable PK with continuous daily dosing, in contrast to
historical experience with ATRA, a non-selective retinoic acid
receptor agonist.”
PK and PD Data from Ongoing Phase 2 Clinical Trial of
SY-1425
Syros presented data based on an evaluation of 45 AML and MDS
patients from the Company’s ongoing Phase 2 clinical trial,
including 36 patients evaluable for PK and 39 patients evaluable
for PD. The data demonstrated that the dosing regimen being used in
the clinical trial achieves blood levels sufficient to elicit a PD
response with evidence of RARα target engagement in patients who
are positive for either the Company’s RARA or IRF8 biomarkers, or
both. The data showed:
- Drug exposures consistent with those
seen in patients with acute promyelocytic leukemia (APL). SY-1425
is approved to treat relapsed or refractory APL in Japan as
Amnolake® (tamibarotene) and has a well-established safety and
efficacy profile in APL. The dosing regimen being used in the Phase
2 trial in RARA or IRF8 biomarker-positive AML and MDS patients is
the same as the dose approved in Japan for APL.
- No significant accumulation or
reduction in SY-1425 exposure after two weeks of continuous dosing,
demonstrating favorable PK properties in comparison to historical
data with ATRA.
- Evidence of RARα target engagement, as
measured by robust and sustained induction of DHRS3 in the majority
of patients evaluated. In preclinical studies, DHRS3 was one of the
most strongly induced genes in response to treatment with SY-1425,
leading to the identification of DHRS3 induction as a PD marker for
use in the trial as an early indicator of whether SY-1425 is
affecting the targeted biology.
- Similar induction of DHRS3 across
patients with relapsed or refractory AML, relapsed or refractory
higher-risk MDS and lower-risk transfusion-dependent MDS.
- Similar induction of DHRS3 across
patients positive for either the RARA or IRF8 biomarkers, or
both.
- Ex vivo myeloid differentiation in a
patient blood sample, confirming downstream functional impact of
target engagement, including dose-dependent induction of CD38, a
marker of cell maturation.
The Phase 2 clinical trial is assessing the safety and efficacy
of SY-1425 as a monotherapy in four AML and MDS patient
populations, as well as in combination with azacitidine, a
standard-of-care therapy, in newly diagnosed AML patients who are
not suitable candidates for standard chemotherapy. All patients
enrolled in the trial are prospectively selected using the
Company’s RARA or IRF8 biomarkers. Additional details about the
trial can be found using the identifier NCT02807558 at
www.clinicaltrials.gov. Syros remains on track to present initial
clinical data from the trial in the fourth quarter of 2017.
Design of Ongoing Phase 1 Clinical Trial of SY-1365 in
Advanced Solid Tumors
In a separate presentation, Syros detailed the design of its
ongoing Phase 1 clinical trial of SY-1365 in patients with advanced
solid tumors, including transcriptionally dependent cancers such as
triple negative breast, small cell lung and ovarian cancers. The
multi-center, open-label trial is expected to enroll approximately
70 patients. The primary objective of the trial is to assess the
safety and tolerability of escalating doses of SY-1365, with the
goal of establishing a maximum tolerated dose and a recommended
Phase 2 dose (RP2D) and regimen. The dose-escalation phase is open
to solid tumor patients for whom standard curative or palliative
measures do not exist or are no longer effective. Following the
dose-escalation phase, an expansion cohort is planned to further
evaluate the safety and anti-tumor activity of SY-1365 in patients
with triple negative breast, small cell lung and ovarian cancers,
and to enroll patients with tumors of any histology in a cohort
focused on analyzing biopsied tumor tissue. SY-1365 target
engagement in peripheral blood mononuclear cells and available
tumor biopsies will be assessed by measuring CDK7 occupancy over
the course of treatment. Additional details about the trial can be
found using the identifier NCT03134638 at
www.clinicaltrials.gov.
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
therapeutic benefit of SY-1425 as a single agent and in combination
with azacitidine; the reporting of initial clinical data from the
ongoing Phase 2 clinical trial of SY-1425 in the fourth quarter of
2017; the ability to identify an appropriate dose and schedule to
support expansion of the Phase 1 clinical trial of SY-1365, and the
benefits of Syros’ gene control platform. 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. Moreover, there can be no assurance that the PK
and PD data generated to date in the ongoing Phase 2 clinical trial
of SY-1425 are predictive of the ability of such trial to meet any
of its endpoints. 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 and 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; replicate scientific and
non-clinical data in clinical trials; successfully develop a
companion diagnostic test to identify patients with the RARA and
IRF8 biomarkers; 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 June 30, 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.
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Media:Syros PharmaceuticalsNaomi Aoki,
617-283-4298naoki@syros.comorInvestors:Stern Investor
Relations, Inc.Hannah Deresiewicz,
212-362-1200hannahd@sternir.com
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