SYRS Syros Pharmaceuticals Inc

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Advancing Novel Treatments for Hematologic Malignancies JP Morgan Conference January 2024 Exhibit 99.1

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Forward-looking statements This presentation contains forward-looking statements (including within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended) concerning Syros and other matters, such as Syros’ clinical development plans, including with respect to tamibarotene, Syros’ ability to deliver benefit to patients and value to stockholders, the timing and impact of upcoming enrollment milestones and clinical data readouts, and the sufficiency of Syros’ capital resources to fund its operating expenses and capital expenditure requirements into the second quarter of 2025. These statements may discuss goals, intentions and expectations as to future plans, trends, events, results of operations or financial condition, or otherwise, based on management’s current beliefs, as well as assumptions made by, and information currently available to, management. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as “may,” “will,” “should,” “would,” “expect,” “anticipate,” “plan,” “likely,” “believe,” “estimate,” “project,” “intend,” and other similar expressions. Statements that are not historical facts are forward-looking statements. Forward-looking statements are based on current beliefs and assumptions that are subject to risks and uncertainties and are not guarantees of future performance. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors, including, without limitation, Syros’ ability to: advance the development of its programs, including tamibarotene, 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 out-licensing arrangements 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.  The foregoing review of important factors that could cause actual events to differ from expectations should not be construed as exhaustive and should be read in conjunction with statements that are included herein and elsewhere, including the risk factors included in Syros’ Annual Report on Form 10-K for the year ended December 31, 2022 and Syros’ Quarterly Report on Form 10-Q for the quarter ended September 30, 2023, each of which is on file with the Securities and Exchange Commission (SEC). Except as required by applicable law, Syros undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise.

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Advancing our vision to deliver on the value of tamibarotene Commercial company delivering new standard of care for frontline treatment of hematologic malignancies Advancing tamibarotene as a potential new standard of care for HR-MDS and AML patients with RARA gene overexpression Preparing for product launch and commercialization Cash runway to fund planned operations into Q2 of 2025 Now Vision

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 Advancing    Tamibarotene:  Potential to  establish new  standard   of care for the  frontline  treatment of  hematologic  malignancies   LARGE MARKET OPPORTUNITIES IN FRONTLINE SETTINGS  Building a focused infrastructure to support targeted patient populations underserved by existing options   MEANINGFUL NEAR-TERM CATALYSTS Upcoming opportunities to build momentum and create value:                pivotal SELECT-MDS-1 data and additional randomized SELECT-AML-1 data, both expected in 2024 ENCOURAGING, CONSISTENT DATA FROM MULTIPLE CLINICAL TRIALS SUPPORT DEVELOPMENT STRATEGY Growing body of evidence in MDS and AML patients with RARA overexpression     $45M FINANCING ADDS TO STRONG CORPORATE POSITION: CASH RUNWAY TO FUND OPERATIONS INTO Q2 OF 2025 

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Multiple near-term value-driving milestones and pre-launch activities underway Last patient enrolled for the pivotal CR data from SELECT-MDS-1 Phase 3 trial Pivotal data from SELECT-MDS-1 Phase 3 trial       Initial data from randomized SELECT-AML-1 trial Dec. 2023 Additional data from randomized SELECT-AML-1 trial 2024 1Q 24 By mid-4Q 24 Tamibarotene in newly diagnosed HR-MDS Tamibarotene in newly diagnosed unfit AML Educating and preparing the treatment community for tamibarotene and RARA overexpression Planning distribution and sales infrastructure  Partnered with Qiagen to ensure RARA testing availability at launch  Pre-launch activities ��

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Tamibarotene: Compelling profile that addresses large targeted populations Tamibarotene is a selective and potent RARa agonist1 1McKeown, Cancer Discovery 2017; 2de Botton S., et al. Blood Advances 2022 ~50% of patients with AML are positive  for RARA overexpression2 ~30%  Normal RARA overexpression with tamibarotene RARA overexpression without tamibarotene of patients with HR-MDS are positive for RARA overexpression2

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Growing body of clinical evidence for tamibarotene in HR-MDS and AML patients with RARA overexpression supports development strategy 1Data presented at ASH 2017, and Syros Data on File; 2de Botton S., et al. Blood Advances 2022; 3Response includes CR, CRi or CRh; 4Data presented by Syros 06Dec2023 Single-agent tamibarotene in R/R HR-MDS patients1  Phase 2 initial randomized data evaluating Tami/Ven/Aza vs. Ven/Aza in ND unfit AML patients4 Phase 2 data evaluating Tami/Aza in  ND unfit AML patients2 Tamibarotene in HR-MDS Tami/Ven/Aza Median time to response: 21 days including one marrow CR 60% Hematologic response1 61% CR/CRi Rate 67% CR in low-blast subset Median time to response3: 1.2 months Median duration of response: 10.8 months Overall survival for complete responders: 18 months 72% Transfusion independence 2023 2017 2020 CR/CRi 70% CR/CRi TREATMENT ARM: Tami/Ven/Aza CONTROL ARM: Ven/Aza 78% CR 22% CRi 30% CR 40% CRi 100% Tamibarotene in AML

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Tamibarotene has demonstrated a well-tolerated safety profile 1Amnolake® post-marketing surveillance data on file; 2Data presented at ASH 2017; 3de Botton S., et al. Blood Advances 2022; 4Data presented at ASH 2022; 5Data presented by Syros 06Dec2023 50% CRi 33% CR Data from randomized portion of SELECT-AML-1 trial Phase 2 trial expected 2023 / 2024 Single agent in AML and MDS patients and doublet (Tami/Aza) in AML patients2,3 Triplet (Tami/Ven/Aza) in AML patients4,5 Safety profile supports use of tamibarotene in combination with azacitidine in MDS and with venetoclax/azacitidine in AML Daily dosing of tamibarotene as a single-agent and in combination with azacitidine has been generally well-tolerated.2-5 No evidence of increased toxicity in combination, with rates of myelosuppression comparable to single-agent azacitidine.2-5  As a triplet, myelosuppression has been comparable to venetoclax + azacitidine4,5 The majority of non-hematologic AEs have been low grade ​and reversible2-5 Well-characterized in over 1,000 acute promyelocytic leukemia (“APL”) patients treated with tamibarotene1

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Significant unmet need in newly diagnosed unfit AML 1 Ferrara F., Clin Lymphoma Myeloma Leuk. 2011; 2DiNardo CD, et al., New England Journal of Medicine, 2020; 3Maiti A., et al., Haematologica, 2021. Acute myeloid leukemia (AML) is a cancer of the blood forming cells in the bone marrow ~50% of the patients are not eligible for intensive treatment and are considered “unfit”1 Venetoclax with azacitidine is standard of care, with a 66% CR/CRi, 37% CR rate and median OS of 14.7 months2 Approximately 1/3 of patients do not respond, and nearly all relapse with a very poor prognosis, median OS of 2.4 months3 Normal AML The standard of care falls short, underscoring the critical demand for improved treatments for newly diagnosed unfit AML patients  

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Randomized portion of trial ~80 patients Tamibarotene + venetoclax + azacitidine Venetoclax + azacitidine randomization (1:1) Safety lead-in completed Ongoing SELECT-AML-1 Phase 2 trial of triplet regimen (Tami/Ven/Aza) in newly diagnosed unfit AML patients with RARA overexpression Key Milestones Initial randomized SELECT-AML-1 clinical data from 23 enrolled patients^ Additional data from randomized SELECT-AML-1 trial Primary endpoint1 CR/CRi rate 2024 �� 1 The study is 80% powered to detect a difference between the CR/CRi rates in the experimental and control arms ^ Data presented by Syros 06Dec2023; Data cut-off was November 13, 2023

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Initial randomized SELECT-AML-1 Phase 2 data in newly diagnosed unfit AML patients with RARA overexpression demonstrate 100% CR/CRi rate CR/CRi Rate 70% CR/CRi Rate 100% CONTROL ARM: Ven/Aza TREATMENT ARM: Tami/Ven/Aza 22% CRi 78% CR CR Rate 78% CR/CRi Rate N=9 30% CR CR/CRi Rate N=10 CR Rate 30% Data presented by Syros 06Dec2023; Data cut-off was November 13, 2023 Initial randomized data builds on previous reported data from the safety lead-in: Tamibarotene in combination with venetoclax and azacitidine was  well tolerated with no new safety signals identified 40% CRi

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Initial randomized SELECT-AML-1 Phase 2 data: Hematologic safety profile shows no additive myelosuppression when combining tamibarotene with Ven/Aza Febrile neutropenia Neutropenia Thrombocytopenia Leukopenia Anemia Hematologic AEs - All Causality Tami/Ven/Aza Safety Population, N=11; Ven/Aza Safety Population, N=12* * Includes 1 patient randomized to Tami/Ven/Aza who received Ven/Aza and discontinued treatment prior to receiving tamibarotene. ^ No low-grade (Grade 1/Grade 2) Hematology AEs were reported for patients in either arm of the study. Preferred Term Regimen TEAEs reported were all Grade 3 or 4 ^ Tami/Ven/Aza Ven/Aza

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1 Greenberg, Blood, 2012; 2Garcia, J et al., Leukemia Research, 2021; 3Elihu Estey, et al., Blood 2022 Higher-Risk MDS (HR-MDS) is closely related to AML Myelodysplastic syndrome (MDS) is also a cancer of the blood forming cells in the bone marrow HR-MDS often is a precursor to AML. More than half of HR-MDS patients progress to AML1 Azacitidine, a hypomethylating agent (HMA), is SOC with a 17% CR rate and a median OS of 18.6 months2 There is a significant need for new therapies - no new therapies beyond HMAs approved since 2006 “MDS-excess blasts” and “AML” essentially form a continuum…Rather than blast percentage, disease categorization may be more accurate if based on biologic features.” – Estey et al., 20223 Precursor States AML HR-MDS LR-MDS

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Ongoing SELECT-MDS-1 Phase 3 trial in newly diagnosed HR-MDS patients with RARA overexpression Robustly designed, double-blind, placebo-controlled study 2:1 randomization Global study with over 120 sites recruiting in 13 countries FDA feedback supports: Focus on population with RARA overexpression CR as primary endpoint for approval (full or accelerated) with supporting data on durability of remission Azacitidine as appropriate comparator Primary endpoint of CR rate is over 90% powered to detect a difference between experimental and control arms with a one-sided alpha of 0.025 Inclusion of OS key secondary endpoint will allow this single trial to efficiently serve as a confirmatory study if needed for full approval Fast Track Designation by the FDA Key Milestones Last patient enrolled for the pivotal CR data from SELECT-MDS-1 Phase 3 trial    1Q 24 Pivotal data from SELECT-MDS-1  Phase 3 trial  SELECT-MDS-1 trial randomization (2:1) Tamibarotene + azacitidine   Placebo + azacitidine Primary endpoint CR rate (190 patients) Key secondary endpoint Overall Survival (OS) (~550 patients) by mid-4Q 24

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Experienced leadership team with proven capabilities and expertise in launching targeted oncology medicines Planning our distribution and sales infrastructure strategy for a launch in the U.S. Targeted patient populations will allow for a focused, specialized sales force Partnered with Qiagen to ensure RARA testing availability Planning our commercial launch in the United States

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Large market opportunities in frontline settings ~25,000 Newly Diagnosed Unfit AML patients in US and EU annually2 Building infrastructure to target synergistic patient populations underserved by existing options ~21,000 Newly Diagnosed HR-MDS patients in the US and EU annually1 ~$4.7B3 MYELODYSPLASTIC SYNDROME (MDS) ACUTE MYELOID LEUKEMIA (AML) PROJECTED MDS GLOBAL MARKET BY 2028: ~$7.5B4 PROJECTED AML  GLOBAL MARKET BY 2028: 1Epidemiology projections from DRG Myelodysplastic Syndromes-Landscape & Forecast-Report 2020 and from DRG Acute Myelogenous Leukemia-Landscape & Forecast-Report 2020;​ 2Epidemiology projections from DRG Acute Myelogenous Leukemia-Landscape & Forecast-Report 2020; 3Evaluate Pharma global market estimate includes all risk groups for MDS; 4Global market estimate includes all AML (fit and unfit)

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Multiple near-term value-driving milestones and pre-launch activities underway Last patient enrolled for the pivotal CR data from SELECT-MDS-1 Phase 3 trial Pivotal data from SELECT-MDS-1 Phase 3 trial       Initial data from randomized SELECT-AML-1 trial Dec. 2023 Additional data from randomized SELECT-AML-1 trial 2024 1Q 24 by mid-4Q 24 Tamibarotene in newly diagnosed HR-MDS Tamibarotene in newly diagnosed unfit AML Educating and preparing the treatment community for tamibarotene and RARA overexpression Planning distribution and sales infrastructure  Partnered with Qiagen to ensure RARA testing availability at launch  Pre-launch activities ��

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Exhibit 99.2

Syros Highlights Anticipated 2024 Milestones to Deliver on the Value of Tamibarotene

— On-Track to Complete Enrollment of 190 patients for Primary Analysis in SELECT-MDS-1 Phase 3 Trial in 1Q 2024;

Pivotal CR Data Expected by Mid-4Q 2024 —

— Additional Data from SELECT-AML-1 Phase 2 Trial Expected in 2024; Initial Data Demonstrated 100% CR/CRi Rate

and Favorable Tolerability Profile —

— Strengthened Balance Sheet with Gross Proceeds of Approximately $45.0 Million from Recent Equity Financing,

Extending Cash Runway into 2Q 2025 —

CAMBRIDGE, Mass., January 8, 2024 – Syros Pharmaceuticals (NASDAQ:SYRS), a biopharmaceutical company committed to advancing new standards of care for the frontline treatment of hematologic malignancies, today highlighted anticipated 2024 milestones to deliver on the value of tamibarotene.

“We are beginning the year with tremendous momentum toward our mission of delivering tamibarotene as a new standard of care for the frontline treatment of hematologic malignancies,” said Conley Chee, Chief Executive Officer of Syros Pharmaceuticals. “Last month, we announced encouraging initial data from the randomized portion of the SELECT-AML-1 Phase 2 trial, which demonstrated a 100% CR/CRi rate and favorable tolerability, strongly supporting continued development in AML and HR-MDS. In addition, we closed an approximately $45.0 million equity financing, providing us additional capital to advance the development of tamibarotene. We are continuing pre-launch activities, including efforts to drive awareness of tamibarotene and of RARA overexpression in support of a future launch.”

Mr. Chee continued, “Following these achievements, we are preparing for an important transformation. By the middle of the fourth quarter of 2024, we expect to report pivotal data from the SELECT-MDS-1 Phase 3 clinical trial. If successful, these data will allow us to file our first New Drug Application and, ultimately, to deliver tamibarotene to the thousands of HR-MDS patients in need of better options. We also plan to report additional data from SELECT-AML-1, which we expect will build on our growing body of clinical evidence and continue to demonstrate a highly differentiated product profile. We look forward to these major milestones as we work to deliver better outcomes to the many HR-MDS and AML patients with RARA overexpression.”

Program Updates and Expected Milestones

Syros is developing tamibarotene, an oral, first-in-class selective retinoic acid receptor alpha (RARα) agonist for the frontline treatment of higher-risk myelodysplastic syndrome (HR-MDS) and acute myeloid leukemia (AML) in patients with RARA gene overexpression. 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.

Syros is currently evaluating tamibarotene in combination with azacitidine in newly diagnosed HR-MDS patients with RARA overexpression in the ongoing SELECT-MDS-1 Phase 3 trial. The primary endpoint of SELECT-MDS-1 is the complete response (CR) rate. Syros expects to complete enrollment of the 190 patients necessary to support the CR primary endpoint analysis in the first quarter of 2024 and to report pivotal CR data by the middle of the fourth quarter of 2024.

Syros is also evaluating tamibarotene in combination with venetoclax and azacitidine in newly diagnosed unfit AML patients with RARA overexpression. In December, Syros announced encouraging initial data from the ongoing randomized SELECT-AML-1 Phase 2 trial, demonstrating a 100% CR/CRi rate in response-evaluable patients treated with the triplet regimen of tamibarotene, venetoclax and azacitidine, as compared to 70% among patients treated with venetoclax and azacitidine alone. The median time to CR/CRi response was rapid; all patients treated with the triplet regimen achieved a CR/CRi by the end of cycle one. Consistent with prior clinical experience reported last

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year, tamibarotene in combination with approved doses of venetoclax and azacitidine was generally well tolerated, and the overall safety profile demonstrated no additive toxicities or new safety signals, and no evidence of increased myelosuppression compared to treatment with the doublet combination of venetoclax and azacitidine. Syros expects to report additional data from SELECT-AML-1 in 2024.

Financial Guidance

Based on its current operating plans, and including gross proceeds of approximately $45.0 million received in its December 2023 equity offering before underwriting discounts and commissions and offering expenses, Syros expects that its existing cash, cash equivalents and marketable securities will be sufficient to fund its anticipated operating expenses and capital expenditure requirements into the second quarter of 2025, beyond the Phase 3 data from the SELECT-MDS-1 trial and additional data from SELECT-AML-1.

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’ clinical development plans, including with respect to the progression of its clinical trials involving tamibarotene and related pre-launch activities, the timing and impact of upcoming clinical data readouts, the timing to complete enrollment of the 190 patients necessary to support the CR primary endpoint analysis in SELECT-MDS-1, the therapeutic potential of tamibarotene, and the sufficiency of Syros’ capital resources to fund its operating expenses and capital expenditure requirements into the second quarter of 2025. 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 September 30, 2023, 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.

Syros Contact

Karen Hunady

Director of Corporate Communications & Investor Relations

1-857-327-7321

khunady@syros.com

Investor Contact

Hannah Deresiewicz

Stern Investor Relations, Inc.

212-362-1200

hannah.deresiewicz@sternir.com

v3.23.4

Document and Entity Information	Jan. 08, 2024
Cover [Abstract]
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Entity Central Index Key	0001556263
Document Type	8-K
Document Period End Date	Jan. 08, 2024
Entity Registrant Name	Syros Pharmaceuticals, Inc.
Entity Incorporation State Country Code	DE
Entity File Number	001-37813
Entity Tax Identification Number	45-3772460
Entity Address, Address Line One	35 CambridgePark Drive
Entity Address, Address Line Two	4th Floor
Entity Address, City or Town	Cambridge
Entity Address, State or Province	MA
Entity Address, Postal Zip Code	02140
City Area Code	(617)
Local Phone Number	744-1340
Written Communications	false
Soliciting Material	false
Pre Commencement Tender Offer	false
Pre Commencement Issuer Tender Offer	false
Security 12b Title	Common Stock, par value $0.001 per share
Trading Symbol	SYRS
Security Exchange Name	NASDAQ
Entity Emerging Growth Company	false

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