-- Conley Chee, CCO and CBO, to succeed Nancy Simonian, M.D. as CEO; Dr. Simonian to retire as CEO, effective December 1, 2023, and will remain on the Board of Directors --

-- Planned workforce reduction of approximately 35% sharpens focus of organization on late-stage development of tamibarotene in MDS and AML and ongoing pre-launch activities --

Syros Pharmaceuticals (NASDAQ:SYRS), a biopharmaceutical company committed to advancing new standards of care for the frontline treatment of hematologic malignancies, today announced a strategic realignment to prioritize key development and pre-launch activities to advance tamibarotene for the frontline treatment of higher-risk myelodysplastic syndrome (HR-MDS) and acute myeloid leukemia (AML). Also today, Syros announced the retirement as Chief Executive Officer (CEO) of Nancy Simonian, M.D., and the appointment of Conley Chee, Syros’ Chief Commercial Officer (CCO) and Chief Business Officer (CBO), as CEO, effective December 2, 2023. Dr. Simonian will remain a member of the Syros Board of Directors following the transition.

“We founded Syros with a singular vision: to translate breakthrough biology into new medicines, with the potential to deliver profound benefit to people living with serious diseases. Over the last ten years, we have made tremendous progress toward this goal, honing our focus on hematologic malignancies and advancing tamibarotene into late-stage development for the frontline treatment of HR-MDS and AML,” said Nancy Simonian, M.D., Chief Executive Officer of Syros. “Today, Syros is at the threshold of an important transformation. As we prepare to report initial data from SELECT-AML-1 later this year and pivotal data from SELECT-MDS-1 next year, we are increasingly focused on building a robust commercial business that can establish tamibarotene as the foundation of care for patients with RARA gene overexpression. It is the right time for me to transition leadership to Conley, an expert at building effective commercial organizations and launching new targeted therapies, as well as a trusted partner who has informed all aspects of our business since joining Syros two years ago.”

Dr. Simonian continued, “Today, we are taking hard – but necessary – steps towards delivering tamibarotene to patients with HR-MDS and AML. This includes streamlining our team and, due to capital constraints, stopping further investment in SY-2101 for the foreseeable future. Together, we expect these decisions will ensure we are sufficiently funded to advance through critical value inflection points. I am deeply grateful to the Syros employees impacted by this reprioritization, who have demonstrated incredible commitment to our company, as well as the patients and families whose lives we aim to improve.”

“I am humbled and excited by the opportunity to lead Syros, building on the strong foundation that Nancy and the team established,” said Conley Chee. “I believe tamibarotene offers a unique and highly differentiated product profile, with the potential to disrupt the treatment paradigm for large populations in MDS and AML, two blood disorders that have largely eluded current targeted approaches. As we look toward near-term data catalysts from SELECT-MDS-1 and SELECT-AML-1, we are planning for our next phase of growth. I am eager to partner with my colleagues to execute our clinical plans, prepare our first new drug application filing, and, ultimately, deliver tamibarotene to the thousands of MDS and AML patients in need of better options.”

Portfolio Update:

Syros is prioritizing the advancement of tamibarotene, its oral first-in-class selective retinoic acid receptor alpha (RARα) agonist for the frontline treatment of HR-MDS and AML. Syros believes tamibarotene – a biologically targeted agent that has demonstrated high complete response rates, a rapid time to response and favorable tolerability across multiple clinical trials to date – has the potential to set a new standard of care for patients with RARA overexpression, which accounts for approximately 50 percent of the HR-MDS and 30 percent of the AML populations.

Tamibarotene is currently being studied in SELECT-MDS-1, a pivotal Phase 3 trial evaluating the combination of tamibarotene and azacitidine in newly diagnosed HR-MDS patients with RARA gene overexpression and in SELECT-AML-1, a Phase 2 trial evaluating the combination of tamibarotene, venetoclax and azacitidine in newly diagnosed unfit AML patients with RARA overexpression.

Syros will stop further investment in the clinical development of SY-2101, its novel, oral form of arsenic trioxide (ATO) for the treatment of newly diagnosed acute promyelocytic leukemia (APL), as well as in its preclinical and discovery-stage programs. Syros may pursue further development of SY-2101 subject to additional capital availability.

Management and Corporate Update:

Syros is streamlining its organization and implementing an approximately 35% workforce reduction to reflect its focus on the clinical development of tamibarotene and potential U.S. commercial launch. Mr. Chee, Syros’s CCO and CBO, will succeed Dr. Simonian as CEO, effective December 2, 2023. He will also join the Company’s Board of Directors upon becoming the CEO.

Mr. Chee joined Syros in 2021. He was most recently at Novartis as Global Head of Oncology Portfolio Management, Global Pipeline Strategy and Precision Medicine. In this role, Mr. Chee contributed to shaping Novartis’ overall pipeline, including driving commercial planning for the company’s early-stage portfolio and diagnostics strategy for oncology. Earlier in his career at Novartis, Mr. Chee served as Vice President – Global Head Oncology Lung Franchise, as well as in multiple US sales and marketing leadership roles. During this time, his work included the U.S. launch of Afinitor, Zykadia, Signifor and the global launches of Tafinlar/Mekinist and Tabrecta. Prior to joining Novartis, Mr. Chee spent five years in roles of increasing responsibility at Pfizer, ultimately serving as Team Leader of International Business Development. He holds an M.B.A. from the Richard Ivey School of Business at the University of Western Ontario and a B.Sc. Pharm. from the University of Alberta and completed his residency in Clinical Pharmacy at the University of British Columbia.

“The Board’s selection of Conley as Syros’ next CEO is the result of thoughtful succession planning, designed to position the company for success in its maturation into a commercial-stage organization while ensuring continuity and empowering our strong leadership team,” said Peter Wirth, Chairman of the Board of Directors of Syros. “On behalf of the Board, I want to thank Nancy for her impactful leadership as CEO. Under her guidance, Syros advanced multiple compounds for the treatment of cancer, with the potential to deliver major advances for thousands of patients globally. I look forward to continuing our partnership on the Board and wish Nancy the very best in her next chapter.”

In addition, and consistent with Syros’ strategic decision to invest its resources solely in advancing tamibarotene through late-stage clinical development to market, Eric Olson, Ph.D., Syros’ Chief Scientific Officer since 2013, will depart Syros effective October 16, 2023.

Dr. Simonian commented, “Eric joined Syros soon after our founding and, in the years since, played a pivotal role in building our gene control platform and advancing our discovery programs from conception to reality. Perhaps most importantly, he and his team made a seminal scientific discovery – identifying the role of RARA overexpression in AML and MDS. As such, he leaves a deep and lasting impact on our company and the patients globally who we hope to treat, and I am deeply grateful to him for his partnership and his many contributions.”

About Syros Pharmaceuticals

Syros is committed to developing new standards of care for the frontline treatment of patients with hematologic malignancies. Driven by the motivation to help patients with blood disorders that have largely eluded other targeted approaches, Syros is developing tamibarotene, an oral selective RARα agonist in frontline patients with higher-risk myelodysplastic syndrome and acute myeloid leukemia with RARA gene overexpression. For more information, visit www.syros.com and follow us on Twitter (@SyrosPharma) and LinkedIn.

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’ leadership transition, strategic reorganization, clinical development and growth plans, the progression of its clinical trials of tamibarotene, the timing and impact of anticipated clinical data, the ability to obtain regulatory approval for tamibarotene and deliver benefit to patients, and the potential to pursue further development of SY-2101. 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 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; sustain the response rates and durability of response seen to date with its drug candidates; successfully develop a companion diagnostic test to identify patients with the RARA biomarker; 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, 2022 and Quarterly Report on Form 10-Q for the quarter ended June 30, 2023, each 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.

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