Syros Pharmaceuticals, Inc. · OTC:SYRS
Syros Pharmaceuticals — Investor Presentation (May 2021)
48 slides from Syros Pharmaceuticals's investor presentation, May 26, 2021
Slide 1: An Expression Makes a World of Difference
An Expression Makes a World of Difference May 2021 Exhibit 99.1
Slide 2: 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 3: Accelerating our vision
Accelerating our vision Targeted hematology therapy franchise Gene control discovery engine Selective CDK inhibitor franchise Fully integrated biopharmaceutical company
Slide 4: Rapidly advancing toward being a commercial-stage company
Rapidly advancing toward being a commercial-stage company Leading gene control platform 3 clinical programs Experienced leadership team Well-funded beyond multiple data readouts 2 potential NDAs in 2024
Slide 5: Advancing a growing clinical-stage pipeline for targeted patient populations
Program Indication Early Clinical IND- Enabling Mid-Clinical Pivotal Pivotal Commercial Rights SY-1425 (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) Select solid tumors Advancing
Slide 6: SY-1425 Selective oral RARα agonist
SY-1425 Selective oral RARa agonist
Slide 7: Clear vision for SY-1425 in RARA-positive cancers
Clear vision for SY-1425 in RARA-positive cancers Now Pivotal trial in MDS Triplet strategy in unfit AML Next NDA in MDS Pivotal trial in AML Commercialization Vision Foundation of care for all RARA+ patients
Slide 8: Compelling data and clear path forward for SY-1425
Compelling data and clear path forward for SY-1425 1de Botton, ASH 2020; 2Fiore, ASH 2020 SY-1425/aza induces high CR rates, rapid onset of action and meaningful durability in RARA+ ND unfit AML1 SY-1425 safety profile supports multiple combination opportunities New translational data suggest RARA b
Slide 9: High CR rates, rapid onset, durability in RARA-positive ND unfit AML
High CR rates, rapid onset of action, and clinically meaningful durability in RARA-positive ND unfit AML 89% of CRs were deep molecular or cytogenetic CRs Responses seen irrespective of mutation or cytogenetic risk Response rates in RARA-negative patients comparable to historical rates for single-ag
Slide 10: Generally well-tolerated combination in ND unfit AML patients
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 aIncludes all enrolled ND unfit patients, N=51. Data presented at ASH 2020 meeting
Slide 11: ND HR-MDS ideal opportunity for SY-1425 with azacitidine
ND HR-MDS represents ideal opportunity for SY-1425 in combination with azacitidine HR-MDS and AML on a disease continuum; distinguished by % blasts in marrow More than half of patients progress to AML1 Neutropenia may lead to infection-related complications, including death2 HR-MDS is closely relate
Slide 12: Ongoing placebo-controlled Phase 3 trial in RARA-positive ND HR-MDS
Ongoing placebo-controlled Phase 3 trial in RARA-positive ND HR-MDS patients 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 RA
Slide 13: New translational data support RARA biomarker
New translational data support the potential for the RARA biomarker to enrich for patients unresponsive to standard of care 30% of patients do not respond to upfront treatment with ven/aza Venetoclax resistance associated with monocytic phenotype,1-3 which includes low BCL2 and high MCL-1 expression
Slide 14: Initiating randomized Phase 2 trial of triplet regimen in unfit AML
Randomized portion of trial ~80 patients SY-1425 + venetoclax + azacitidine Venetoclax + azacitidine randomization (1:1) Safety lead-In ~15 patients Initiating randomized Phase 2 trial of triplet regimen in ND RARA-positive unfit AML patients Plan to also evaluate triplet as salvage strategy for pat
Slide 15: ND HR-MDS and unfit AML represent significant market opportunities
ND HR-MDS and unfit AML represent significant market opportunities ~30% of all AML and MDS patients are RARA-positive Newly diagnosed HR-MDS ~15,000 new cases annually in US and EU Expected to grow into $1B+ market No new approved agents, aside from HMAs, in a decade Existing options offer limited e
Slide 16: SY-2101 Novel oral form of arsenic trioxide
SY-2101 Novel oral form of arsenic trioxide
Slide 17: Our vision for SY-2101
Our vision for SY-2101 Now Acquired asset Next Registration-enabling study Commercialization Vision Standard of care for APL patients
Slide 18: SY-2101: Highly synergistic with our targeted heme franchise
SY-2101: Highly synergistic with our advancing targeted heme franchise Strategic opportunity as we accelerate toward becoming a commercial-stage company Potential to become standard of care in APL Novel oral capsule of arsenic trioxide (ATO) Clinical-stage asset with opportunity for accelerated appr
Slide 19: IV ATO is transformative for APL but heavy treatment burden
IV ATO is transformative therapy for APL patients but comes with heavy treatment burden >80% Cure rates IV ATO oral ATRA Significant opportunity to reduce treatment burden, increase access and reduce health care costs and utilization Current course of treatment involves up to 140 two- to four-hour i
Slide 20: Opportunity for SY-2101 to become standard of care
Opportunity for SY-2101 to become standard of care in significant market APL is ~10 % of AML Newly diagnosed APL Genetic fusion of RARA and PML genes ~2,000 patients diagnosed in US and Europe annually1,2 ~$250 million overall market opportunity based on current pricing for IV ATO3 Opportunity to be
Slide 21: Completed Phase 1 PK study of SY-2101
Completed Phase 1 PK study of SY-2101 Ravandi et al 2020 Haematologica Trisenox (arsenic trioxide) USPI Three dosing cohorts: 5, 10 and 15 mg orally Once daily 12 patients with advanced hematologic malignancies Median age: 76.5 Prior lines of therapy: Up to 5 Generally well-tolerated with low-grade
Slide 22: Advancing SY-2101 toward registration-enabling Phase 3 trial
Advancing SY-2101 toward registration-enabling Phase 3 trial FDA feedback supports: Molecular CR as primary endpoint for accelerated approval Event-free survival (EFS) as primary endpoint for full approval Dose confirmation study SY-2101 + ATRA Pivotal Phase 3 Trial ~150 newly diagnosed APL patients
Slide 23: SY-5609 Selective oral CDK7 inhibitor
SY-5609 Selective oral CDK7 inhibitor
Slide 24: Our vision for SY-5609
Our vision for SY-5609 Now Phase 1 trial Initial combination with fulvestrant Next Phase 1 expansion Additional combinations Vision Transformative targeted therapy for difficult-to-treat cancers
Slide 25: CDK7i disrupts CDK and transcriptional activity
CDK7i disrupts the CDK and transcriptional activity needed to progress through the cell cycle Altered Rb pathway Activating mutations in cell signaling CDK1 CDK2 Selective CDK7 inhibition attacks two fundamental processes in cancer Cell Cycle Transcription CDK7i MYC MYB MCL1 MCL1 Apoptosis CDK7i has
Slide 26: Three-pronged development strategy for SY-5609
Three-pronged development strategy to maximize potential of SY-5609 Compelling preclinical data + Strong mechanistic rationale + High unmet need Leveraging Rb pathway alterations Overcoming CDK4/6 resistance Exploiting transcriptional and cell cycle dependencies
Slide 27: Rb alterations associated with deeper, more sustained responses
Rb alterations associated with deeper and more sustained responses in preclinical studies of breast, lung and ovarian cancers 29% of basal breast cancer patients1 ~1/3 of HR+ breast cancer patients post CDK4/6 inhibitors2 75-90% of small cell lung cancer patients3 67% of high-grade serous ovarian ca
Slide 28: SY-5609 induces robust responses in preclinical HR+ breast cancer models
Overcoming treatment resistance: SY-5609 induces robust responses in preclinical HR+ breast cancer models Palb: palbociclib, 50mg/kg once daily, oral; Flv: fulvestrant, 2.5mg/kg once weekly, sub-cutaneuous, SY-5609: 6 mg/kg once daily, oral CDK4/6 inhibitor resistant model CDK4/6 inhibitor and hormo
Slide 29: Robust responses in preclinical colorectal and pancreatic models
Targeting dependencies on transcription and cell cycle control induces robust responses in preclinical colorectal and pancreatic cancer models 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 CRC dat
Slide 30: Ongoing Phase 1 dose-escalation trial in select solid tumors
Dose-escalation Cohort extensions in select populations HR+ breast cancer, post CDK4/6 Expansion Further explore SY-5609 as single and combination agent Advanced solid tumors Single agent Combination with fulvestrant Ongoing Phase 1 dose-escalation trial in select solid tumors Advanced solid tumor p
Slide 31: SY-5609 biological activity and clinical activity
SY-5609 induced biological activity associated with tumor regressions in preclinical models and clinical activity with first-generation CDKi Data presented in October 2020 at EORTC-NCI-AACR Virtual Symposium AEs predominantly low grade; most frequent related AEs include nausea, diarrhea, fatigue, pl
Slide 32: Gene Control Discovery Engine
Gene Control Discovery Engine
Slide 33: Regulatory regions of the genome control gene expression
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 Redefinin
Slide 34: Robust early-stage pipeline to fuel long-term growth
Therapeutic Area Program Target Development Drug Discovery IND-Enabling Commercial Rights Cancer CDK12 inhibitor Target 1 Target 2 Myeloproliferative neoplasms Monogenic Disease Sickle cell disease & beta thalassemia Myotonic dystrophy type 1 Robust early-stage pipeline to fuel long-term growth Syro
Slide 35: Multiple expected value-driving milestones and strong cash position
Multiple expected value-driving milestones and strong cash position SY-5609 SY-2101 SY-1425 w/ aza SY-1425 w/ ven+aza Initiate Phase 3 registration trial in ND HR-MDS Potential NDA filing in ND HR-MDS 2024 Initiate Phase 2 trial w/ safety lead-in in ND unfit AML2H 2021 Initial data from Phase 2 tria
Slide 36: Rapidly advancing toward our vision
Rapidly advancing toward our vision Progressing into pivotal studies Preparing for product launches Platform fueling robust pipeline Fully integrated company with medicines that provide a profound benefit for patients Advancing growing clinical-stage pipeline Capital to fund planned operations into
Slide 37: Appendix
Appendix
Slide 38: SY-1425: Novel, first-in-class RARα agonist
1425 SY-1425 binds to RARα and activates differentiation genes SY-1425: Novel, first-in-class RARα agonist with broad combination potential RARa Aza cross links to DNA SY-1425 enhances apoptosis preclinically Apoptosis DNA damage Gene control platform identifies novel patient subset Distinct MOA, to
Slide 39: RARA is not a prognostic biomarker in AML patients
RARA is not a prognostic biomarker in AML patients Analysis of BeatAML Registry RARA expression and survival1 1 Tyner et al., Functional Genomic Landscape of Acute Myeloid Leukaemia, Nature 2018 2 TCGA Research Network, Genomic and Epigenomic Landscapes of Adult De Novo Acute Myeloid Leukemia, NEJM
Slide 40: SY-1425/azacitidine activity in RARA-positive R/R AML
SY-1425/azacitidine combination: Clinical activity observed in heavily pretreated RARA-positive R/R AML ORR of 19% (4/21) with 2 responding patients continuing on treatment at months 8 and 9, respectively 1 CRc 2 CRi 1 MLFS Higher ORR of 43% (3/7) in HMA and ven naïve patients Transfusion independen
Slide 41: SY-5609: Highly selective and potent oral CDK7 inhibitor
SY-5609: Highly selective and potent oral CDK7 inhibitor 0.06 nM potency for CDK7 13,000- to 49,000-fold more selective for CDK7 over CDK2, CDK9 and CDK12 Only 4 of 485 kinases inhibited at ≥ 90% 100-91% Inhibition 90-80% Inhibition 79-71% Inhibition Induced apoptosis in cancer cells but not in non-
Slide 42: SY-5609: Tumor growth inhibition below MTD in preclinical models
SY-5609: Tumor growth inhibition observed below MTD in preclinical models Regressions observed at 5-fold below MTD of ≥10 mg/kg QD Triple negative breast cancer model Dashed lines represent end of treatment Data presented in October 2019 at EORTC-NCI-AACR Conference Vehicle 1 mg/kg BID 2 mg/kg QD 3
Slide 43: SY-5609: Dose-dependent tumor growth inhibition and PD effects
0 0.3 1 3 6 9 12 12 mg/kg SY-5609: Dose-dependent tumor growth inhibition and PD effects in tumor tissue in preclinical colorectal cancer models Dose-dependent increase in POLR2A Tumor growth inhibition Dose-dependent decrease in E2F1 Data presented in May 2020 at ASCO Virtual Symposium Dose-depende
Slide 44: SY-5609: Safety overview from early dose-escalation data
SY-5609: Safety overview from early dose-escalation data (n=17) Single Agent Adverse Events; All Causality Patients (%) Single Agent Related Adverse Events Patients (%) Predominantly low grade; most frequent related AEs include nausea, diarrhea, fatigue, platelet count decrease and vomiting DLTs: na
Slide 45: SY-1365: Peri-infusional AEs in Phase 1 trial
1H2H1H 2H 53 mg/m2 64 mg/m2 SY-1365: Peri-infusional AEs in Phase 1 trial were associated with peak blood concentrations and not CDK7 target engagement Longer infusions maintained CDK7 target engagement while lowering peak drug concentrations and decreasing frequency and severity of peri-infusional
Slide 46: Applying platform to sickle cell disease and beta thalassemia
Applying our platform to monogenic diseases: sickle cell disease and beta thalassemia SCD and beta thalassemia caused by mutated adult globin gene Fetal globin gene typically turned off at birth In some SCD and beta thalassemia patients, fetal globin stays on and is associated with milder disease Cl
Slide 47: SY-2101 transaction overview and $90.5 million strategic financing
SY-2101 transaction overview and $90.5 million strategic financing Asset acquisition Upfront cash payment of $12 million Additional regulatory milestone of $6 million in APL indication Aggregate sales milestones of up to $10 million Strategic financing Completed strategic financing yielding $90.5 mi
Slide 48: SYR2:S
SYR2:S
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