An Expression Makes a World of Difference December 2022 Exhibit 99.1

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, SY-2101 and SY-5609, Syros’ ability to deliver benefit to patients and value to stockholders, the timing and impact of upcoming clinical and preclinical data readouts, the timing for submitting a new drug application to the Food and Drug Administration, and the sufficiency of Syros’ capital resources to fund its operating expenses and capital expenditure requirements into 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, SY-2101 and 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 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.  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, 2021 and Syros’ Quarterly Report on Form 10-Q for the quarter ended September 30, 2022, each of which is on file with the Securities and Exchange Commission (SEC). In addition, the extent to which the COVID-19 pandemic continues to impact our workforce and our discovery research, supply chain and clinical trial operations activities, and the operations of the third parties on which we rely, 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. 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.

SIGNIFICANT MARKET OPPORTUNITIES IN FRONTLINE Targeting patient populations underserved by existing options, which are commercially synergistic MULTIPLE NEAR-TERM CATALYSTS Upcoming opportunities to build momentum and create value, which include pivotal SELECT-MDS-1 data, randomized SELECT-AML-1 data and initiation of Phase 3 trial in APL TARGETED HEMATOLOGY PORTFOLIO Advancing clinical trials in frontline MDS, AML and APL with the potential to set new standards-of-care, supported by a growing body of data STRONG CORPORATE POSITION Cash runway to fund operations into 2025 Developing new standards-of-care for the frontline treatment of hematologic malignancies 3 clinical programs from our hematology portfolio MDS AML APL

Program Indication  Early Clinical IND- Enabling Mid-clinical Pivotal Pivotal Commercial Rights Tamibarotene (oral RARα agonist) Newly diagnosed HR-MDS (w/aza) Newly diagnosed unfit AML (w/ven+aza) SY-2101 (oral ATO) Newly diagnosed APL (w/ATRA) SY-5609  (oral CDK7 inhibitor) Metastatic pancreatic cancer (w/chemo) Colorectal cancer (w/atezolizumab)* Advancing our diversified clinical pipeline Tamibarotene is approved in Japan as Amnolake® for patients with relapsed/refractory APL *Roche-sponsored trial  Americas, Europe, Australia, Israel & Russia SELECT-AML-1 Trial Dose confirmation study Safety Lead-In SELECT-MDS-1 Trial Ph1/1b Ph3 2H 2023 Seeking partnership opportunities

PK and safety data Initiation of Phase 3 trial 2H 2023 Multiple value-driving milestones Development candidate named from CDK12 program SY-5609 SY-2101 in APL Tamibarotene in HR-MDS Tamibarotene in AML Pivotal data from SELECT-MDS-1 Phase 3 trial 4Q23/1Q24 Potential NDA filing 2024 Clinical activity data from safety lead-in SELECT-AML-1 trial Initiation of randomized portion of the SELECT-AML-1 trial   1Q23          Data from randomized SELECT-AML-1 trial 2023/2024 Clinical activity data from pancreatic cancer safety lead-in Discovery

Tamibarotene Selective oral RAR    agonist

Value of Tamibarotene Selective and potent RAR    agonist; ~50% of MDS patients and ~30% of AML patients are positive for RARA gene overexpression Clinical development strategy informed by consistent data from multiple trials demonstrating encouraging clinical activity and safety profile Oral drug with novel mechanism and favorable tolerability profile support use in combination and in frontline treatment for those unfit to receive chemotherapy Ongoing Phase 3 trial in newly diagnosed HR-MDS and Phase 2 trial in newly diagnosed unfit AML patients with RARA overexpression Targeting a multi-billion-dollar opportunity in HR-MDS and AML

Clinical development strategy reinforced by encouraging, consistent data from multiple trials  Single-agent tamibarotene in R/R HR-MDS patients with RARA overexpression showed 60% hematologic response, including one marrow CR1  Phase 2 data evaluating tamibarotene with azacitidine in ND unfit AML patients with RARA overexpression showed: 61% CR/CRi rate2 67% CR rate in low blast count subset Data from SELECT-AML-1 safety lead-in evaluating tamibarotene with venetoclax and azacitidine in ND unfit AML patients with RARA overexpression showed: 83% CR/CRi rate3 Safety profile supports ability to use full doses of tamibarotene in combinations with azacitidine in MDS and with venetoclax/azacitidine in AML 1 Data presented at ASH 2017; 2 Data presented at ASH 2020; 3 Data presented at ASH 2022 Growing body of clinical evidence for tamibarotene Pivotal data from SELECT-MDS-1 Phase 3 trial expected late 2023 / early 2024 Tamibarotene in HR-MDS Tamibarotene in AML Data from randomized portion of SELECT-AML-1 trial Phase 2 trial expected 2023 / 2024 ✓ ✓ ✓ ✓

High CR rates, rapid onset of action, and clinically meaningful durability in Phase 2 trial* in newly diagnosed unfit AML with RARA overexpression 89% of CRs were deep molecular or cytogenetic CRs Responses seen irrespective of mutation or cytogenetic risk Response rates in patients negative for RARA overexpression were comparable to historical rates for single-agent aza1-3 67% of low blast count AML patients achieved CR with tamibarotene/aza 27% of low blast count AML patients negative for RARA overexpression achieved CR *Phase 2 trial evaluating tamibarotene/azacitidine Data from 18 response evaluable patients with RARA overexpression and 28 response evaluable patients negative for RARA overexpression presented at ASH 2020 meeting Data from 6 response-evaluable low blast count AML patients with RARA overexpression and 11 response evaluable low blast count AML patients negative for RARA overexpression presented at ASH 2020 meeting 1Dombret, Blood 2015; 2Fenaux, JCO 2010; 3Thepot, American Journal of Hematology 2014

Safety profile supports multiple combinations and long-term use, enhancing opportunity* Generally well-tolerated combination in ND unfit AML patients No increase in neutropenia, anemia and thrombocytopenia compared to single-agent aza Majority of non-hematologic AEs are low grade and reversible *Phase 2 trial evaluating tamibarotene/azacitidine; data presented at ASH 2020 aIncludes all enrolled ND unfit patients, N=51.

Ongoing SELECT-MDS-1 Phase 3 trial in newly diagnosed HR-MDS patients with RARA overexpression Robustly designed, double-blind, placebo-controlled study 90% power to detect a difference in CR rates between experimental and control arms 2:1 randomization with one-sided alpha of 0.025 FDA feedback supports: Focus on population with RARA overexpression CR as primary endpoint for approval Azacitidine as appropriate comparator Key Milestones Phase 3 data 4Q23/1Q24 Potential NDA filing 2024 SELECT-MDS-1 trial 190 patients randomization (2:1) Tamibarotene + azacitidine   Placebo + azacitidine Primary endpoint CR rate

Syros’ Product Candidate Targets ~50% of patients Syros is developing potentially the first therapy for a targeted population in HR-MDS Tamibarotene has the potential to set a new treatment paradigm for HR-MDS patients with RARA overexpression Physicians are familiar with companion diagnostics to determine optimal treatment for AML à Anticipate rapid adaption of targeted therapy in HR-MDS Targeted Population All Comers Population N/A  Azacitidine or decitabine - offers limited efficacy  COMPETITIVE LANDSCAPE OF APPROVED THERAPIES ~50% are Positive for RARA overexpression ~21,000 newly diagnosed HR-MDS patients in US and EU estimated annually Patients positive for RARA overexpression Tamibarotene + aza NOTE: RARA-positivity based on Syros data on file from Study SY-1425-201 and the SELECT-MDS-1 Study (27May2022) from over 175 patients with MDS Sources: Decision Resources Group, NCCN guidelines,  *Evaluate Pharma market estimate includes all risk groups for MDS MDS represents a ~$3.3B* market by 2026​

Randomized portion of trial* ~80 patients Tamibarotene + venetoclax + azacitidine Venetoclax + azacitidine randomization (1:1) Safety lead-In ~ 6-15 patients Ongoing SELECT-AML-1 Phase 2 trial of triplet regimen (Tami/Ven/Aza) in ND unfit AML patients with RARA overexpression Also evaluating triplet as salvage strategy for patients in control arm who do not respond to ven/aza Key Milestones Safety lead-in data Randomized data 2023/2024 Primary endpoint Composite CR rate Translational data support potential for RARA overexpression biomarker to enrich for patients more likely to respond to tamibarotene, for whom the standard of care is suboptimal 30% of patients do not respond to upfront treatment with ven/aza and a majority of those with initial response ultimately relapse Venetoclax resistance is associated with monocytic phenotype 1-3; most patients with RARA overexpression, including those who achieved CR/CRi in tamibarotene trial, have this monocytic phenotype4 1Zhang, Nature 2018; 2Kuusanmäki, Haematologica 2019; 3Pei, Cancer Discovery 2020; 4Fiore, ASH 2020

Safety Lead-in of SELECT-AML-1 trial: Safety and response summary CR = complete response; CRi = CR with incomplete hematologic recovery; ​ CR/CRi Rate N=6 Median Time to CR/CRi 33 days (range 25–88 days) 50% CRi 33% CR 4/5 patients with CR/CRi had high monocytic expression score (MES) associated with venetoclax resistance  Safety Summary: Myelosuppression is comparable to reports of venetoclax + azacitidine in this population​ The majority of non-hematologic AEs are low grade ​and reversible SAEs were reported in 6 patients; the most frequent (occurring in ≥ 2 pts) included febrile neutropenia (4 pts) and pneumonia (3 pts) Median duration of therapy was 76.5 days (20-104); Median duration of follow-up was 107 days (56-314) Data presented at ASH 2022 CR/CRi Rate 83%

Tamibarotene targets patients with RARA overexpression which represents one of the largest targeted populations in unfit AML Targeted Populations All Comers Populations ~30% are positive for RARA overexpression LDAC + glasdegib HMA1 + venetoclax XOSPATA®  (r/r) FLT3+ TIBSOVO ® IDH1+ IDHIFA® IDH2+ Targets ~8% of patients Targets ~11% of patients Targets ~30% of patients ~1/3 of patients do not respond to standard of care ven/aza and majority of those with initial response ultimately relapse. ~25,000 Newly Diagnosed Unfit AML Patients in US and EU  Epidemiology: DRG.  Market sizing: Evaluate Pharma  NOTE*: market estimate includes all AML (fit and unfit) Prevalence of RARA-positive patients based on data presented at ESH 2017 and ESH 2019; Resistant Ven population - Dinardo, NEJM 2020; Dinardo, Blood 2019 Prevalence and Clinical Effect of IDH1 and IDH2 Mutations Among Cytogenetically Normal Acute Myeloid Leukemia Patients, Clin Lymphoma Myeloma Leuk. 2015 Sep;15(9):550-5. Daver N, Schlenk RF, Russell NH, et al. Targeting FLT3 mutations in AML: review of current knowledge and evidence. Leukemia. 2019;33(2):299–312.  COMPETITIVE LANDSCAPE OF APPROVED THERAPIES Syros’ Product Candidate Targets ~30% of patients RARA-positive Tamibarotene + ven/aza  Newly diagnosed AML represents a ~$6.6 billion* market by 2025

SY-2101 Novel oral form of arsenic trioxide

Novel oral form of arsenic trioxide (ATO) with opportunity to replace standard of care for APL patients; APL is approximately 10% of all AML patients Orally bioavailable with exposures consistent with IV ATO Clear development path to approval in front-line APL Potential for rapid adoption in front-line APL, including specialized commercial effort and synergies with tamibarotene Value of SY-2101

Clear development path in frontline APL Based on preliminary data as of July 2022 from dose confirmation study:       The first cross-over data directly comparing SY-2101 to the approved dose of IV ATO SY-2101 administered at 15 mg achieved exposures comparable to IV ATO administered at 0.15 mg/kg based on Cmax and AUC parameters SY-2101 showed high oral bioavailability of ~80% Continues to support favorable tolerability and safety profile FDA feedback from November 2021 supports: Molecular CR as primary endpoint compared to historic data for accelerated approval  Event free survival (EFS) as primary endpoint compared to historic data for full approval IV ATO arm for safety comparison In July 2022, received feedback from EMA, which together with prior FDA feedback, informs decision to move forward with single registration trial that could support approval of 2101 in the US and EU Phase 3 trial in frontline APL ~215 patients randomization (2:1) SY-2101 + ATRA   IV ATO + ATRA Primary endpoints  Molecular CR rate and EFS in comparison to historical IV ATO data Dose confirmation study ~6 to 24 APL patients Key Milestones Initiation of Phase 3 trial  2H 2023

SY-2101 offers significant opportunity to reduce treatment burden, increase access, reduce health care costs and utilization Current standard of care IV ATO oral ATRA >80% Cure rates Treatment burden: Current course of treatment involves infusions of Market opportunity for an oral therapy: APL accounts for ~10% of all adult AML cases diagnosed in US and Europe annually  ~2,000 patients are diagnosed with APL in the US and EU annually NCCN AML treatment guidelines (Nov 2020) Trisenox (arsenic trioxide) USPI up to 140 x 2-4 hrs over nearly a year

SY-5609 Highly selective and potent oral CDK7 inhibitor

Cell Cycle SY-5609: Highly selective and potent oral CDK7 inhibitor SY-5609 is highly selective with subnanomolar potency2 1MTD not yet reached as of October 2022 2Marineau JJ et al, 2021, Discovery of SY-5609: A Selective, Noncovalent Inhibitor of CDK7, J Med Chem Data presented in October 2019 at EORTC-NCI-AACR Conference Transcription CDK7i MYC MYB MCL1 MCL1 Apoptosis Altered Rb pathway BRAF and KRAS mutations CDK1 CDK2 Transcription Transcription CDK4/6 M G2 S G1 Apoptosis Phase 1 study in pancreatic cancer and select solid tumor patients demonstrates promising clinical activity MTD not yet reached with optimized dosing1, and dose escalation is continuing Well tolerated safety profile in combination with predominantly low grade AEs; Broad potential in multiple difficult to treat cancer populations, including PDAC and CRC 100-91% Inhibition 90-80% Inhibition 79-71% Inhibition

Clinical activity including a confirmed PR and emerging exposure-response relationships in ongoing Phase 1 single agent and combination cohorts *Gemcitabine and nab-paclitaxel administered at approved doses Well tolerated safety profile; MTD has not been reached 30 patients dosed across five levels (4 to 10 mg), with only 1 DLT (4 mg dose level/grade 3 diarrhea) Clinical activity observed, including 2/2 response evaluable patients with SD at 10 mg, w/ 1 PDAC patient with 10% tumor reduction Emerging exposure-response relationship Well tolerated safety profile; MTD has not been reached  AE profile consistent with single agent SY-5609 or gemcitabine monotherapy or gemcitabine/nab-paclitaxel One patient with confirmed PR and 98% reduction CA-19-9 at the 4 mg 5609 dose level in combination with gemcitabine 50% (4/8) DCR in patients treated at 4 and 5 mg levels in combination with gemcitabine Emerging exposure-response relationship, with PR patient demonstrating higher-than-average exposure for the dose administered Continued dose escalation of SY-5609 to 15 mg as a single agent and to 10 mg with gemcitabine planned Single Agent – Dose Escalation from 4 mg to 10 mg Combination: SY-5609 starting at 4 mg w/gemcitabine +/- nab-paclitaxel* Patient population Relapsed/refractory patients with select solid tumors Dose escalation to evaluate safety, tolerability, and signs of clinical activity Patient population Metastatic patients who have progressed following treatment with FOLFIRINOX Safety lead in cohorts to evaluate safety, tolerability, and signs of clinical activity Optimized Dosing Schedule: SY-5609 administered 7d on/7d off Data as of October 2022

Preclinical data support SY-5609 in BRAF-mutant CRC in combination with PDL1 inhibitor: SY-5609 part of Roche’s Phase 1/1b INTRINSIC trial 67% (20/30) of models demonstrated ≥ 50% TGI 23% (7/30) demonstrated deep responses of ≥ 90% TGI Deep responses enriched in BRAF-mutant (5/10) models Robust anti-tumor activity in BRAF-mutant CRC as single agent 0 10 Days 20 0 500 1000 1500 2000 Tumor Volume (mm3) 2500 30 Vehicle SY-5609 (6mpk QD) CDK7 inhibition enhances anti-tumor activity of PD-1 inhibition1 CDK7 inhibitor induces DNA replication stress and genome instability in cancer cells, triggering immune-response signaling In animal models, CDK7 inhibitor enhances tumor response to anti-PD1 immunotherapy Prolonging overall survival, and increasing immune cell infiltrates CRC data presented in May 2020 at ASCO Virtual Symposium. 1. Zhang et al., 2020, Cancer Cell 37, 1-18 First clinical investigation of CDK7 inhibitor with an immunotherapy Key Milestones: Roche is now actively enrolling patients in the arm of its ongoing Phase 1/1b INTRINISIC trial evaluating SY-5609 in combination with atezolizumab       - Roche is the sponsor of the trial and Syros is supplying  SY-5609

Gene Control Discovery Engine

Previously unexplored regulatory regions of the genome control expression of genes determining cell function; majority of disease variation found in these regions 98% Patient Impact Medicines that control the expression of genes to provide profound benefit for patients with severe diseases Redefining the power of small molecules to control expression of genes ! Regulatory Genomics Disease Biology Transcriptional Chemistry

PARTNERED PROGRAMS Program Target Development Drug Discovery IND-enabling Commercial Rights Sickle cell disease & beta thalassemia Myeloproliferative neoplasms Seeking partnerships for our oncology discovery programs ONCOLOGY Program  Target Development Drug Discovery  IND-enabling Commercial Rights CDK12 inhibitor CDK11 inhibitor WRN inhibitor

Rapidly advancing toward our vision Preparing for product launches Commercial company with medicines that provide a profound benefit for cancer patients Advancing late-stage targeted hematology pipeline Capital to fund planned operations into 2025 Now Next Vision