Syros Pharmaceuticals, Inc. · OTC:SYRS
Syros Pharmaceuticals — Investor Presentation (January 2018)
33 slides from Syros Pharmaceuticals's investor presentation, Jan 8, 2018
Slide 1: Forward-looking statements
Forward-looking statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this presentation, inc
Slide 2: Our Vision
To create unparalleled value for patients, employees and shareholders by creating transformative medicines for severe disease through our world-leading expertise in gene control and our exceptional people and culture Our Vision
Slide 3: Syros: productive, pioneering, strong foundation, broad impact
Syros Productive Advancing 1 IND every other year on average Pioneering First platform dedicated to the regulatory genome Strong foundation Broad strategic optionality driven by experienced leadership team Broad impact Platform applicable across a wide array of diseases with focus on cancer, I/O and
Slide 4: 2018 objectives and milestones; recent accomplishments
Advance — Leverage platform to Build on fundamentals for first-in-class clinical fuel pipeline evolution toward fully programs integrated company 18 objectives and milestones SY-1425 + Select new development candidate + Continue to build out development + Report clinical data on azacitidine and + Ad
Slide 5: Gene expression, controlled by non-coding genome, is central to cell function
Gene expression, controlled by non-coding genome, is central to cell function in health and disease Human genome Coding region (2% of genome) Non-coding region (98% of genome) Controls expression of genes to determine function of all cells Alterations involved in wide range of diseases Unexploited f
Slide 6: Our platform integrates three areas of expertise
Our platform integrates three areas of expertise Cancer Modulate transcription regulators to drive apoptosis or differentiation Immuno-oncology Modulate tumor cells, macrophages and T cells to promote tumor killing Monogenic diseases Target regulatory elements to modulate expression of known gene Re
Slide 7: Transcriptional small molecule chemistry and regulatory genomics
Transcriptional Regulatory small molecule genomics chemistry Whole genome Biochemical, structural biology analysis to identity and medicinal chemistry dysregulated genes in Disease biology expertise in targeting patient subsets transcription Single gene analysis Proprietary gene control to identify
Slide 8: Growing pipeline of multiple first-in-class programs
Program Indication Discovery Preclinical Early Clinical Mid-Clinical Pivotal Commercial Rights SY-1425 (RAR agonist) Frontline AML (combination with azacitidine) Syros (North America and Europe) R/R AML and HR MDS (combination with daratumumab) Breast cancer SY-1365 (CDK7 inhibitor) Solid tumors dos
Slide 9: SY-1425 (RAR agonist): Turning on differentiation genes in cancer
SY-1425 (RAR agonist): Turning on differentiation genes in cancer First-in-class selective, oral RAR agonist Novel AML and MDS subsets and biomarkers discovered by Syros In Phase 2 trial in combination with azacitidine and daratumumub Data expected 2H 2018 Single-agent activity and myeloid different
Slide 10: Phase 2 trial evaluating SY-1425 combinations in AML and MDS
Ongoing Phase 2 trial evaluating SY-1425 combinations in genomically defined AML and MDS patients All patients selected based on RARA and IRF8 biomarkers Two distinct combinations in difficult-to-treat AML and MDS populations Expect to report clinical data on both combinations in second half of 2018
Slide 11: Clinical and biologic activity seen with single agent SY-1425
Clinical and biologic activity seen with single agent SY-1425 in difficult to treat AML and HR MDS patients Generally well-tolerated with manageable and/or reversible side effects 58 R/R AML or HR MDS and LR MDS patients treated for median duration of 80 days; patients treated up to 8 months and rem
Slide 12: Differentiation observed in biomarker-positive patient samples and trial patients
Differentiation observed in biomarker-positive patient samples and clinical trial patients treated with SY-1425 Myeloid differentiation starting after one cycle, with marrow blast reduction >25% beginning after two cycles and continuing to the start of the fourth cycle 66-year-old male with R/R AML
Slide 13: Clinical activity observed in relapsed/refractory patients
Clinical activity observed in relapsed/refractory patients Initial response observed two weeks after starting treatment and lasting through five months without blood transfusions Erythroid response in R/R HR MDS patient Marrow CR in R/R HR MDS patient Initial responses (platelet and ANC) observed on
Slide 14: SY-1425 and AZA combination induces greater, more durable response
SY-1425 and AZA combination induces greater, more durable response than either drug alone and induces apoptosis preclinically *Internal data on file Combo leads to deeper and more durable response in preclinical PDX model Combo induces apoptosis in RARA-high cell lines* “Clinical Pharmacodynamic Mar
Slide 15: SY-1425 with daratumumab induces immune-mediated cell death
SY-1425 in combination with daratumumab induces immune-mediated cell death “SY-1425, a selective RAR agonist, induces high levels of CD38 expression in RARA-high AML tumors creating a susceptibility to anti-CD38 therapeutic antibody treatment” SY-1425 induces CD38 cell surface expression SY-1425 ind
Slide 16: Significant need for well-tolerated oral therapies in AML and MDS
Significant need for well-tolerated oral therapies that extend survival and improve quality of life Newly diagnosed, unfit >50% of AML patients ineligible for standard chemo upon diagnosis HMAs/ less intensive therapies with modest efficacy are standard-of-care Survival of < 12 months Relapsed or re
Slide 17: Unique mechanism and tolerability profile support combination potential
Unique mechanism and tolerability profile support combination potential RARA and IRF8 biomarkers and SY-1425 opportunity cut across mutational landscape Unique mechanism points to potential for combinations with chemo and targeted agents without anticipated overlapping toxicities ~20% FLT3+ ~33% RAR
Slide 18: Current and future opportunities for SY-1425 in AML and HR MDS
Current and future opportunities for SY-1425 within AML and HR MDS treatment landscape Source: Health Advances interviews and analysis, SEER 2015, UpToDate 2015, Fernandez HF 2010 ASH, Ohtake S 2004 Blood. SY-1425 current targeted segments AML Patients Unfit AML R/R AML HR MDS Patients Fit AML HR MD
Slide 19: SY-1365 (CDK7 inhibitor): Controlling expression of tumor-driving genes
SY-1365 (CDK7 inhibitor): Controlling expression of tumor-driving genes First-in-class selective inhibitor of CDK7 Lowers expression of key tumor-driving genes, transcription factors and anti-apoptotic proteins CDK7 inhibition induces apoptosis and preferentially kills cancer cells over non-cancerou
Slide 20: CDK7 inhibition: powerful approach to target transcriptionally driven cancers
Reduced expression of oncogenic transcription factors Cell death CDK7 inhibition: powerful approach to target transcriptionally driven cancers Transcriptional addiction: certain cancers become dependent on increased expression of disease-driving transcription factors CDK7 is a key player in driving
Slide 21: SY-1365 is a first-in-class potent and selective CDK7 inhibitor
SY-1365 is a first-in-class potent and selective CDK7 inhibitor Covalent Highly potent Enzymatic IC50 = 22 nM Cellular IC50 < 20 nM Highly selective Greater than 30-fold selective for CDK7 over CDK9 and CDK2 Only binds to 7 out of 468 kinases screened at >90% binding Sustained PD effect (~3-day half
Slide 22: Dose escalation ongoing in Phase 1 trial of SY-1365
Dose escalation ongoing in Phase 1 clinical trial of SY-1365; expansion to initially focus on ovarian cancer (OC) Expect to present data from dose escalation phase of trial in second half of 2018 Safety, PK/PD, proof-of-mechanism Expansion phase to focus on ovarian cancer Robust anti-tumor activity
Slide 23: Significant need for therapies in advanced high-grade serous ovarian cancer
Significant need for therapies that improve survival in advanced high-grade serous ovarian cancer Platinum sensitive 55-60% are sensitive or partially sensitive to platinum Progress after 6 to 12 months Despite initial responses, majority of patients relapse within 3 to 5 years Platinum resistant 30
Slide 24: Preclinical data support SY-1365 as single agent and in combination
Preclinical data support potential of SY-1365 as single agent and in combination in additional cancers SY-1365 enhances response to venetoclax in CDX model of AML “BCL2L1 (BCLXL) expression and MYC super-enhancer positivity predict sensitivity to the covalent CDK7 inhibitor SY-1365 in Triple Negativ
Slide 25: Immuno-oncology strategy: modulate tumor and immune cells
Immuno-oncology strategy: modulate tumor and immune cells to pro-inflammatory state to promote tumor killing Immune cell type Change IFNg CD14 naive -- CD14 naïve* 21x M1* 61x M2* 6x M2 + inhibitor* 61x *denotes addition of activated CD8 cells Analyzed regulatory genomes of tumor and immune cells(br
Slide 26: Monogenic disease strategy: Sickle Cell Disease
mRNA Monogenic disease strategy: Target regulatory elements to modulate the expression of a known gene Sickle Cell Disease (SCD) Clinical and genetic data point to therapeutic benefit of elevated fetal globin Using our platform to develop small molecules to control globin expression Sickle Globin Ge
Slide 27: Sickle Cell Disease (SCD)
Sickle Cell Disease (SCD) SCD caused by mutated globin gene Fetal form typically turned off at birth In some SCD patients, the fetal globin gene remains on and is associated with milder disease eet “ pay Pay vnnnnnvns age panne Fetal Sickle Globin Gene Gene + Developed detailed maps of globin expres
Slide 28: Collaboration with Incyte for myeloproliferative neoplasms targets
Leveraging our platform in collaboration with Incyte to discover novel targets for myeloproliferative neoplasms Option to obtain exclusive worldwide rights for up to seven validated targets Responsible for drug discovery, development and commercialization Exclusive worldwide commercialization rights
Slide 29: Strategic collaborations and in-licensing
Strategic Collaborations In-licensing Pursuing strategic collaborations to maximize potential of our gene control platform Programs Continue to drive SY-1425 and SY-1365 to key value inflection points Assess partnerships post value inflections Platform Leverage gene control platform for target and d
Slide 30: Investment balanced across clinical pipeline and discovery
Investment balanced across clinical pipeline and discovery to achieve short- and long-term goals Drive SY-1425 and SY-1365 to key value creating milestones Maintain investment in discovery with goal to: Deliver one IND every other year on average Build on leadership in gene control Cash runway into
Slide 31: Rapidly advancing toward our vision
Rapidly advancing toward our vision SYRS launched Seminal gene control publications Gene control platform established Proof of principle in oncology Research organization established 2015 SY-1425 in ongoing Phase 2 trial SY-1365 enters clinical development Initiated first monogenic disease program M
Slide 32: 2013 2015 2017 2018 goals 2019 vision
2013 2015 2017 2018 goals 2019 vision Preparing for commercialization Leveraging our platform with strategi collaborations ‘Advancing our clinical pipeline enhancing our gene control platform to fuel a sustainable pipeline " S¥RSiounched + Gone conte "-SY-42Sinongoing + SY-1425combinaion _-2inesioge
Slide 33: SYR2:S
SYR2:S
Syros Pharmaceuticals — Investor Presentation (January 2018) on 6ix