Updated Dose-Escalation Data Demonstrate
Clinical Activity in Heavily Pre-treated Patients Across Multiple
Tumor Types
Plan to Initiate Expansion Evaluating SY-5609
in Combination with Chemotherapy in Pancreatic Cancer in 4Q
2021
Plan to Initiate Phase 1b Trial Evaluating
SY-5609 in Combination with a BTK Inhibitor in Mantle Cell Lymphoma
in 1H 2022
Evaluating SY-5609 in Combination with
Immunotherapy in BRAF-Mutant Colorectal Cancer in Roche’s Ongoing
Phase 1/1b INTRINSIC Trial
Management to Host Conference Call at 4:00 p.m.
ET Today
Syros Pharmaceuticals (NASDAQ:SYRS), a leader in the development
of medicines that control the expression of genes, today announced
new data from the dose-escalation portion of the Phase 1 clinical
trial of SY-5609, its highly selective and potent oral
cyclin-dependent kinase 7 (CDK7) inhibitor, demonstrating clinical
activity at tolerable doses as a single agent across multiple tumor
types. The data is being presented today in an oral presentation at
the 2021 ESMO Congress.
“I am encouraged by the results from this dose-escalation
study,” said Manish R. Sharma, M.D., Associate Director of Clinical
Research at START Midwest in Grand Rapids, Michigan, and an
investigator in the Phase 1 study of SY-5609. “This trial enrolled
heavily pretreated patients with some of the most
difficult-to-treat malignancies. Notably, the prolonged stable
disease and tumor shrinkage seen in pancreatic cancer patients is
distinct from what you would expect to see in this highly
refractory patient population – particularly when treated with a
single agent. Based on these results, together with preclinical
data supporting combination strategies, I believe SY-5609 has the
potential to provide a meaningful benefit for patients with cancers
that have largely eluded treatment to date.”
“The new data presented today demonstrate proof-of-activity for
SY-5609 and point to an optimal dosing regimen with a tolerability
profile that is amenable to multiple combination approaches,” said
David A. Roth, M.D., Chief Medical Officer of Syros. “As we move
into this next stage of development, we are introducing a
three-pronged strategy to maximize the potential of SY-5609 and
drive to proof-of-concept in combination with chemotherapy, a
targeted therapy and an immunotherapy in both solid tumors and
blood cancer. We believe this approach could unlock significant
opportunities for SY-5609 and achieve the transformative potential
of CDK7 inhibition for people with difficult-to-treat cancers.”
Dose-Escalation Data Demonstrate Clinical Activity Across
Multiple Tumor Types The Phase 1 multi-center, open-label
dose-escalation study of SY-5609 enrolled patients with advanced
breast, colorectal, lung, ovarian and pancreatic cancers, as well
as patients with solid tumors of any histology harboring Rb pathway
alterations. Patients were treated in cohorts exploring continuous
daily dosing as well as intermittent dosing regimens, including
seven days on treatment and seven days off (7d on/7d off) and five
days on treatment and two days off (5d on/2d off).
As of July 6, 54 patients treated with single-agent SY-5609 in
the study were eligible for a safety analysis and 45 patients were
evaluable for clinical response. The median age of patients
enrolled in the study was 65.5. Patients had been heavily
pre-treated with as many as eight prior therapies and a median of
four prior therapies.
Safety, Tolerability, Dose and Schedule
- Across all doses and schedules, the majority of adverse events
(AEs) were low-grade and reversible. The most common
treatment-emergent AEs were nausea, diarrhea, thrombocytopenia,
fatigue and anemia.
- Low rate of discontinuations due to AEs.
- Tolerability was optimized with 7d on/7d off schedule, which
had lowest rates of treatment-emergent AEs, while demonstrating
comparable rates of stable disease (SD) as seen with more
dose-intense regimens, supporting the selection of this schedule
for further development of SY-5609.
- The maximum tolerated dose (MTD) of the 7d on/7d off schedule
has not yet been reached.
- Changes in POLR2A mRNA expression, a pharmacodynamic (PD)
marker for CDK7 inhibition, were associated with anti-tumor
activity and were sustained for at least three days following drug
cessation, supporting intermittent dosing.
Early Clinical Activity Data
- Thirteen patients (28.9%) achieved SD, with tumor regressions
of up to 20% in six of those patients, across multiple tumor
types.
- The most substantial clinical activity was observed in heavily
pre-treated patients with advanced pancreatic cancer.
- Five of 13 (38.5%) evaluable patients achieved SD, with tumor
reductions in two of those patients.
- Reductions in the CA 19-9 tumor marker, which is used in
clinical practice to monitor tumor progression, were observed in
three of four pancreatic cancer patients with serial CA 19-9 data.
These reductions ranged from 32% to 72%.
- Notably, one metastatic pancreatic cancer patient who had
failed two prior lines of therapy and relapsed after a third line
of treatment experienced prolonged SD of up to 10 months.
- Analysis of clinical activity by tumor type and mutational
status supports the mechanistic rationale for SY-5609 in Rb-altered
and KRAS-mutant cancers.
Clinical Development Plans for SY-5609 in Solid Tumors and
Blood Cancer Further development of SY-5609 will explore three
combination regimens, focusing initially on indications with
compelling clinical and/or preclinical activity, as well as a
strong mechanistic rationale and high unmet need.
Syros plans to initiate an expansion cohort evaluating SY-5609
in combination with chemotherapy for the treatment of pancreatic
cancer in the fourth quarter of 2021. Syros also plans to initiate
a Phase 1b trial evaluating SY-5609 in combination with a Bruton’s
tyrosine kinase (BTK) inhibitor for the treatment of mantle cell
lymphoma in the first half of 2022. Syros plans to employ a 7d
on/7d off dosing schedule in both of these trials. In addition, as
announced in August 2021, Syros entered into an agreement with
Roche to explore SY-5609 in combination with atezolizumab in
patients with BRAF-mutant colorectal cancer in Roche’s ongoing
Phase 1/1b INTRINSIC trial.
New Preclinical Data Further Support Planned Expansion
Strategy Syros also presented new preclinical data at ESMO
evaluating the anti-tumor and PD activity of intermittent dosing
regimens for SY-5609, as well as new preclinical data evaluating
SY-5609 as a single agent and in combination with chemotherapy in
pancreatic cancer models. Taken together, these data further
support Syros’ dose expansion strategy, including the decision to
use a 7d on/7d off dosing schedule and combine with chemotherapy in
patients with pancreatic cancer. The data showed that SY-5609:
- Induced robust anti-tumor activity as a single agent in ovarian
cancer models that was maintained at higher doses on intermittent
schedules, including a 7d on/7d off schedule. POLR2A PD effects
were sustained in tumor tissue through 72 hours post-dosing,
consistent with what was observed in patients in the
dose-escalation study.
- Induced regressions as a single agent in half (4/8) of the
pancreatic cancer models that were studied, including models
derived from heavily pre-treated patients.
- Resulted in deeper responses when combined on 7d on/7d off
schedule with gemcitabine in KRAS-mutant pancreatic models than
either agent alone.
Conference Call Information Syros will host a conference
call at 4:00 p.m. ET today to discuss these data, as well as the
design of its dose expansion study. To access the live conference
call, please dial 866-595-4538 (domestic) or 636-812-6496
(international), and refer to conference ID 4648345. A webcast of
the call will also be available on the Investors & Media
section of the Syros website at www.syros.com. An archived replay
of the webcast will be available for approximately 30 days
following the conference call.
About Syros Pharmaceuticals Syros is redefining the power
of small molecules to control the expression of genes. Based on its
unique ability to elucidate regulatory regions of the genome, Syros
aims to develop medicines that provide a profound benefit for
patients with diseases that have eluded other genomics-based
approaches. Syros is advancing a robust clinical-stage pipeline,
including: tamibarotene, a first-in-class oral selective RARα
agonist in RARA-positive patients with higher-risk myelodysplastic
syndrome and acute myeloid leukemia; SY-2101, a novel oral form of
arsenic trioxide in patients with acute promyelocytic leukemia; and
SY-5609, a highly selective and potent oral CDK7 inhibitor in
patients with select solid tumors and blood cancers. Syros also has
multiple preclinical and discovery programs in oncology and
monogenic diseases.
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 Syros’s clinical
development plans and collaborations with respect to SY-5609, the
anticipated timing to expand or initiate new clinical trials of
SY-5609, the evaluation of SY-5609 in combination with other
therapies, and the ability of SY-5609 to have a benefit for
patients. 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 SY-5609 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 SY-5609; sustain the response
rates seen to date with SY-5609; replicate scientific and
non-clinical data in clinical trials; successfully establish a
patient selection strategy and develop a companion diagnostic test
to identify patients most likely to benefit from SY-5609; 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’ Annual Report on Form 10-K for the year ended
December 31, 2020 and Quarterly Report on Form 10-Q for the quarter
ended June 30, 2021, each of 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. In addition, the extent to which the COVID-19 pandemic
continues to impact Syros’ workforce and its clinical trial
operations activities, and the operations of the third parties on
which Syros relies, will depend on future developments, which are
highly uncertain and cannot be predicted with confidence, including
the duration and severity of the pandemic, additional or modified
government actions, and the actions that may be required to contain
the virus or treat its impact. 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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version on businesswire.com: https://www.businesswire.com/news/home/20210920005292/en/
Media: Naomi Aoki Syros Pharmaceuticals 617-283-4298
naoki@syros.com
Investor: Hannah Deresiewicz Stern Investor Relations,
Inc. 212-362-1200 hannah.deresiewicz@sternir.com
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