POLR2A

REC-617, a precision designed molecule, demonstrated dose-linear pharmacokinetics (PK) with rapid absorption and robust pharmacodynamic (PD) biomarker modulation, suggesting substantial target engagementConfirmed partial response (PR) observed during monotherapy dose-escalation in a patient with platinum-resistant ovarian cancer, treated with 4 lines of prior therapy in advanced setting, durable response ongoing after more than 6 months of treatmentAdditional 4 patients demonstrated a best response of stable disease (SD) for up to 6 months of treatmentPlans to continue monotherapy dose escalation and initiate combination studies in 1H 2025 SALT LAKE CITY, Dec. 09, 2024 (GLOBE NEWSWIRE) -- Recursion (Nasdaq: RXRX) reported initial monotherapy dose-escalation data from the Phase 1/2 study (ELUCIDATE) of REC-617, a selective CDK7 inhibitor, in advanced solid tumors. These results were presented today after market close at an AACR Special Conference in Cancer Research. The company will also hold a webinar on December 10 at 6:30 AM MT / 8:30 AM ET / 1:30 PM GMT to present the preliminary data broadcast from Recursion’s X (formerly Twitter), LinkedIn, and YouTube accounts with an opportunity to submit questions here. "Cell cycle dysregulation and transcriptional 'addiction' are both hallmarks of many aggressive cancers," said David Hallett, Ph.D., Chief Scientific Officer of Recursion. "By inhibiting CDK7, we have the potential to target both mechanisms while fine tuning the therapeutic index. Using our precision design platform, we created a molecule with rapid oral absorption to reduce GI tissue exposure, a suitable half life to manage side effects, and target engagement covering the IC80 level." ELUCIDATE is an ongoing Phase 1/2 study evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and maximum tolerated dose (MTD) of REC-617 in patients with advanced solid tumors. As of the November 15, 2024 data cutoff, preliminary findings include 18 patients with advanced solid tumors who were response evaluable in the monotherapy dose-escalation phase. Doses ranged from 2 mg to 20 mg once daily (QD) and 1 mg twice daily (BID). REC-617 was generally well-tolerated across all dose levels, with no discontinuations due to adverse events (AEs). Adverse events to date were predominately Grade 1-2, on-target, and reversible. An MTD has not yet been reached. While efficacy was not an endpoint in this Phase 1 study, or anticipated in monotherapy, a confirmed durable partial response (PR) by RECIST on REC-617 monotherapy was achieved in a patient with metastatic, platinum-resistant ovarian cancer. The response is on-going after more than 6 months of treatment. This patient had progressed following 4 lines of prior therapy in the advanced setting. In addition, four patients achieved a best response of stable disease (SD) across multiple dose levels for up to 6 months of treatment. "These initial findings for REC-617 represent an exciting step forward in the development of CDK7 inhibitors, with a favorable PK/PD profile and a durable confirmed partial response observed in dose escalation in a highly pre-treated patient population," said Najat Khan, Ph.D., Chief R&D Officer and Chief Commercial Officer, Recursion. "Designed using our AI-powered OS platform, REC-617 reflects our focus on enhancing the therapeutic index to deliver more effective and safer treatment options for patients. We are eager to continue this momentum in dose escalation and to initiate the next phase of the program next year." In parallel to the ongoing monotherapy dose escalation (QD and BID), combination studies are expected to initiate for ELUCIDATE in H1, 2025. The company expects to present additional ELUCIDATE as well as preclinical REC-617 data at future medical meetings. Summary of Interim REC-617 Monotherapy Dose Escalation Results Study Design & Demographics Phase 1 monotherapy dose escalation in advanced solid tumorsData cutoff as of November 15, 2024 - 19 patients enrolled (18 response evaluable)Heavily pre-treated population (median of 4 prior lines of therapy in the advanced setting)Antiemetics and anti-diarrheals not mandated prophylaxis for nausea/vomiting/diarrhea PK/PD Summary REC-617 exceeds CDK7 IC80 with rapid absorption (Tmax 0.5–2 hours) with a half-life of 5-6 hoursEarly POLR2A 3-4x modulation suggests ~80–90% target engagementQuick, time-limited target engagement with POLR2A normalization in 24 hoursTwice-daily (BID) dosing under investigation Safety Profile/AE Summary Adverse events (AEs) were predominantly low grade, on-target, and reversible upon treatment cessationEarly data indicates a favorable safety profile – maximum tolerated dose (MTD) not reachedNo treatment discontinuations due to AEs3 treatment related serious adverse events (SAE)s reported in 2/19 patientsEvents resolved and treatment continued after dose reductionAntiemetics and anti-diarrheals not mandated prophylaxis for nausea/vomiting/diarrhea Confirmed Partial Response & Stable Disease Summary One confirmed partial response (PR) by RECIST 1.1 (decrease of more than 30% in the sum of the longest diameters of target lesions + no new lesions + no progression of non target lesions) Partial response (-34%) achieved with reduction of 2 lymph nodes (para-aortic and mesenteric) at Week 16 with normalization of LDHReduction of tumor marker CA125 from 1249 to 694 kU/L (-44%)Reduction of tumor marker TK1 from 174 to 56 DuA (-68%)Response ongoing after more than 6 months of treatmentPatient continues study therapy without need for antiemetics Four additional patients achieved durable (up to 6 months of treatment) response of stable disease (SD) as best response across multiple dose levels All four patients progressed prior to entering the studyThree CRC patients (6L-7L) and one NSCLC patient (4L)One patient on 2mg QD and three patients on 10mg QD About REC-617REC-617 is a potential best-in-class CDK7 inhibitor, precision designed using AI-led approaches, with only 136 novel molecule synthesized from hit to candidate identification in less than 12 months. The molecule is designed to maximize its therapeutic index by enabling the tight control of both the extent and duration of target inhibition. CDK7 inhibition combines many potential benefits such as transcription inhibition, reduction of aberrant kinome activation, cell cycle inhibition, and modulation of estrogen receptor activity. This makes it an attractive target to overcome common resistance pathways associated with CDK4/6 inhibition, which only targets the cell cycle. About ELUCIDATEREC-617 is currently being evaluated as a monotherapy in the ELUCIDATE trial. ELUCIDATE is a multicenter, open-label, two-stage clinical trial to evaluate safety, pharmacokinetics, pharmacodynamics, and efficacy of REC-617 in advanced solid tumors, including non-small cell lung cancer (NSCLC), colorectal cancer, breast cancer, pancreatic cancer, ovarian cancer, head and neck cancer. Both the monotherapy and combination therapy dose escalation portion of the trial will enroll patients across multiple dose levels to determine the optimal biological dose (OBD). The dose expansion phase of the trial will commence upon identification of the OBD. The primary efficacy endpoint of the expansion phase is objective response rate (ORR). About RecursionRecursion (NASDAQ: RXRX) is a clinical stage TechBio company leading the space by decoding biology to radically improve lives. Enabling its mission is the Recursion OS, a platform built across diverse technologies that continuously generate one of the world’s largest proprietary biological and chemical datasets. Recursion leverages sophisticated machine-learning algorithms to distill from its dataset a collection of trillions of searchable relationships across biology and chemistry unconstrained by human bias. By commanding massive experimental scale — up to millions of wet lab experiments weekly — and massive computational scale — owning and operating one of the most powerful supercomputers in the world, Recursion is uniting technology, biology and chemistry to advance the future of medicine. Recursion is headquartered in Salt Lake City, where it is a founding member of BioHive, the Utah life sciences industry collective. Recursion also has offices in Toronto, Montréal, New York, London, Oxford area, and the San Francisco Bay area. Learn more at www.Recursion.com, or connect on X (formerly Twitter) and LinkedIn. Media ContactMedia@Recursion.com Investor ContactInvestor@Recursion.com Forward-Looking Statements This document contains information that includes or is based upon “forward-looking statements” within the meaning of the Securities Litigation Reform Act of 1995, including, without limitation, those regarding the potential efficacy of REC-617; timing of the Phase 1/2 clinical trial of REC-617; early and late stage discovery, preclinical, and clinical programs; licenses and collaborations; prospective products and their potential future indications and market opportunities; Recursion OS and other technologies; business and financial plans and performance; and all other statements that are not historical facts. Forward-looking statements may or may not include identifying words such as “plan,” “will,” “expect,” “anticipate,” “intend,” “believe,” “potential,” “continue,” and similar terms. These statements are subject to known or unknown risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statements, including but not limited to: challenges inherent in pharmaceutical research and development, including the timing and results of preclinical and clinical programs, where the risk of failure is high and failure can occur at any stage prior to or after regulatory approval due to lack of sufficient efficacy, safety considerations, or other factors; our ability to leverage and enhance our drug discovery platform; our ability to obtain financing for development activities and other corporate purposes; the success of our collaboration activities; our ability to obtain regulatory approval of, and ultimately commercialize, drug candidates; our ability to obtain, maintain, and enforce intellectual property protections; cyberattacks or other disruptions to our technology systems; our ability to attract, motivate, and retain key employees and manage our growth; inflation and other macroeconomic issues; and other risks and uncertainties such as those described under the heading “Risk Factors” in our filings with the U.S. Securities and Exchange Commission, including our Annual Report on Form 10-K and Quarterly Reports on Form 10-Q. All forward-looking statements are based on management’s current estimates, projections, and assumptions, and Recursion undertakes no obligation to correct or update any such statements, whether as a result of new information, future developments, or otherwise, except to the extent required by applicable law.

Protein arginine methyltransferases (PRMTs) are catalytic enzymes for arginine methylation, capable of methylating a variety of proteins and playing pivotal roles in biological processes such as gene expression, splicing, and DNA damage repair.  Currently, 9 members of the PRMTs family has been identified, divided into three major types. Type I, catalyzes the formation of asymmetric dimethylarginine and includes PRMT1, PRMT2, PRMT3, PRMT4, PRMT6, PRMT8. Type II catalyzes the formation of symmetric dimethylarginine and includes PRMT5 and PRMT9. Type III is responsible for the formation of monomethylarginine and includes only PRMT7.  PRMT5 is the most highly studied subtype of PRMT, forming a heterooctameric complex with Methylosome protein 50 (MEP50), enabling the symmetrical dimethylation of a variety of substrates, including histone and non-histone proteins. PRMT5 histone substrates primarily include H4 residue Arg3 (H4R3), H3 residue Arg2 (H3R2), Arg8 (H3R8), and H2A residue Arg3 (H2AR3), whose symmetric dimethylation is related to gene transcription regulation. Non-histone substrates of PRMT5 include Sm proteins, nucleolar proteins, RAF proteins, EGFR, androgen receptor (AR), tumor suppressor p53, IL-2, HOXA9, NFkB, KLF4, GATA4, PDCD4, E2F-1, SPT5, GM130, POLR2A, SREBP1a, Rad9, and more that are involved in regulating cellular signalling, differentiation, DNA repair, and mRNA splicing among other cellular processes.  Research has found that PRMT5 is overexpressed in various types of cancer, such as glioblastoma, melanoma, leukemia/lymphoma, multiple myeloma, prostate cancer, bladder urothelial carcinoma, ovarian cancer, lung cancer, gastric cancer, and colorectal cancer. Furthermore, PRMT5 expression is associated with a poor prognosis in tumor progression and metastasis. Further research has shown that PRMT5 directly affects the growth and differentiation of tumor cells by regulating multiple genes such as p53, IL-2, TRAIL receptor, MITF, transcription factor E2F-1, and tumor suppressor gene 7. Additionally, PRMT5 has been found to constitute "synthetic lethal" partnerships with gene mutations like methylthioadenosine phosphorylase (MTAP), metabolic enzyme methionine adenosyltransferase 2 alpha (MAT2A), and others.  Both in vitro and in vivo studies have shown that inhibition or knockdown of PRMT5 significantly reduces cell proliferation, migration, and colony formation, but promotes apoptosis and cell cycle arrest. Furthermore, oral PRMT5 inhibitors demonstrate significant antitumor activity in lung tumor xenograft models. Thus, PRMT5 has become a new target for the development of epigenetic anti-cancer drugs. PRMT5 Competitive LandscapeAccording to the data provided by Patsnap Synapse-Global Drug Intelligence Database: the following figure shows that as of 22 Sep 2023, there are a total of 41 PRMT5 drugs worldwide, from 39 organizations, covering 28 indications, and conducting 20 clinical trials. 👇Please click on the picture link below for free registration or login directly if you have freemium accounts, you can browse the latest research progress on drugs , indications, organizations, clinical trials, clinical results, and drug patents related to this target. Based on the analysis of target PRMT5, it can be concluded that several companies, including GSK Plc, Ipsen SA, Tango Therapeutics, Inc., Amgen, Inc., Mirati Therapeutics, Inc., and Prelude Therapeutics, Inc., are actively involved in the research and development of drugs targeting PRMT5. These companies have drugs in various stages of development, with some reaching advanced stages such as Phase 2. The indications for these drugs cover a wide range of cancer types, indicating the potential of PRMT5 as a therapeutic target. Small molecule drugs and chemical drugs are the most rapidly progressing drug types under the target PRMT5, with small molecule drugs being the primary focus. The United States, China, and Canada are the countries/locations with the highest development activity, with the United States leading in Preclinical stage and China showing progress in Phase 1. Overall, the current competitive landscape suggests a promising future for the development of PRMT5 inhibitors in the pharmaceutical industry. PRMT5 inhibitors entering Phase II clinical studies: GSK-3326595GSK-3326595 is a small molecule drug that is being developed by Epizyme, Inc. It is designed to target PRMT5, a protein involved in various cellular processes. The drug is being investigated for its potential therapeutic applications in neoplasms, immune system diseases, and hemic and lymphatic diseases. The active indications for GSK-3326595 include solid tumors, non-Hodgkin lymphoma, neoplasms, acute myeloid leukemia, and myelodysplastic syndromes. These are all serious and potentially life-threatening conditions that affect different parts of the body, including the blood, lymph nodes, and various organs. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. Currently, GSK-3326595 is in Phase 2 of clinical development, which means that it has already undergone initial testing in humans and has shown promising results in terms of safety and efficacy. Phase 2 trials typically involve a larger number of participants and aim to further evaluate the drug's effectiveness and side effects. As a small molecule drug, GSK-3326595 has the advantage of being able to penetrate cells and interact with specific targets, such as PRMT5. This targeted approach can potentially lead to more effective treatment options with fewer side effects compared to traditional chemotherapy or radiation therapy. Epizyme, Inc. is the originator organization behind GSK-3326595. They are a biopharmaceutical company focused on developing novel therapies for patients with genetically defined cancers and other diseases. With their expertise in epigenetics and targeted therapies, Epizyme is dedicated to advancing the field of biomedicine and improving patient outcomes. In summary, GSK-3326595 is a small molecule drug being developed by Epizyme, Inc. It targets PRMT5 and has potential applications in neoplasms, immune system diseases, and hemic and lymphatic diseases. The drug is currently in Phase 2 of clinical development and shows promise in treating solid tumors, non-Hodgkin lymphoma, acute myeloid leukemia, and myelodysplastic syndromes. Epizyme, Inc. is the organization behind the development of this innovative drug, aiming to provide new treatment options for patients in need. PRMT5 inhibitors entering PhaseⅠ/Ⅱclinical studies: AMG-193AMG-193 is a small molecule drug developed by Amgen, Inc. It falls under the therapeutic areas of neoplasms and respiratory diseases, specifically targeting PRMT5. The drug is primarily indicated for the treatment of non-small cell lung cancer and solid tumors. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. Amgen, Inc. is the originator organization behind AMG-193. Being a small molecule drug, AMG-193 is designed to interact with PRMT5, a target protein involved in various cellular processes. By specifically targeting PRMT5, the drug aims to inhibit its activity and potentially disrupt the growth and survival of cancer cells in non-small cell lung cancer and solid tumors. Neoplasms, or abnormal tissue growth, encompass a wide range of cancers. Non-small cell lung cancer is one of the most common types of lung cancer, accounting for approximately 85% of all cases. Solid tumors, on the other hand, refer to abnormal masses of tissue that can occur in various organs, such as the breast, colon, or prostate. The current development stage of AMG-193, Phase 1/2, suggests that the drug has undergone initial testing in a small group of patients to evaluate its safety, dosage, and potential efficacy. This phase typically involves assessing the drug's pharmacokinetics, side effects, and preliminary therapeutic effects. The fact that AMG-193 has obtained IND approval in China indicates that it has met the necessary regulatory requirements to proceed with clinical trials in the country. In summary, AMG-193 is a small molecule drug developed by Amgen, Inc. that targets PRMT5. It is indicated for the treatment of non-small cell lung cancer and solid tumors. The drug has reached Phase 1/2 on a global scale and has obtained IND approval in China, allowing for further clinical trials in the country.

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 CAMBRIDGE, Mass.--(BUSINESS WIRE)-- 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 pro 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 . 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 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.