Syros Pharmaceuticals, Inc. · OTC:SYRS
Syros Pharmaceuticals — Investor Presentation (January 2022)
33 slides from Syros Pharmaceuticals's investor presentation, Jan 10, 2022
Slide 1: An Expression Makes a World of Difference
An Expression Makes a World of Difference January 2022 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: Selective CDK Inhibitor Portfolio, Targeted Hematology Portfolio, Gene Control Engine
SELECTIVE CDK INHIBITOR PORTFOLIO Advancing in indications where there is a high unmet need as well as strong clinical/preclinical data and mechanistic rationale 3 clinical programs from our hematology and CDK portfolios, as well as a robust gene control discovery engine TARGETED HEMATOLOGY PORTFOLI
Slide 4: Significant clinical progress and upcoming data readouts
SY-5609 Significant clinical progress and upcoming data readouts position us well to achieve our vision 2021 2022 2023/24 ✓ Initiation of SY-2101 dose confirmation study • • PK and safety data from SY-2101 dose confirmation study in mid-2022 Initiation of SY-2101 Phase 3 trial in 1Q 2023 SY-2101 ✓ I
Slide 5: Advancing our diversified clinical pipeline
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 can
Slide 6: Tamibarotene: Selective oral RARa agonist
Tamibarotene Selective oral RARa agonist
Slide 7: Value of Tamibarotene
Value of Tamibarotene Selective and potent RARa agonist; ~30% of AML and HR-MDS patients are RARA-positive Ongoing Phase 3 trial in newly diagnosed HR-MDS, potentially the first therapy for a targeted population in HR-MDS with broad potential in RARA-positive patients Oral drug with novel mechanism
Slide 8: High CR rates in Phase 2 RARA-positive unfit AML
High CR rates, rapid onset of action, and clinically meaningful durability in Phase 2 trial in RARA-positive newly diagnosed 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
Slide 9: Safety profile supports multiple combinations and long-term use
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 aIncl
Slide 10: Ongoing SELECT-MDS-1 Phase 3 trial in HR-MDS
Ongoing SELECT-MDS-1 Phase 3 trial in RARA-positive newly diagnosed HR-MDS 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 RARA
Slide 11: Syros' Product Candidate Targets ~30% of patients
Syros’ Product Candidate Targets ~30% 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 RARA-positive HR-MDS patients Physicians are familiar with companion diagnostics to determine opt
Slide 12: SELECT-AML-1 Phase 2 trial of triplet regimen
Randomized portion of trial ~80 patients Tamibarotene + venetoclax + azacitidine Venetoclax + azacitidine randomization (1:1) Safety lead-In ~15 patients Ongoing SELECT-AML-1 Phase 2 trial of triplet regimen in ND RARA-positive unfit AML patients Also evaluating triplet as salvage strategy for patie
Slide 13: Tamibarotene targets one of the largest targeted populations in unfit AML
Tamibarotene targets RARA-positive patients which represents one of the largest targeted populations in Unfit AML Targeted Populations All Comers Populations ~30% are RARA-positive LDAC + glasdegib HMA1 + venetoclax XOSPATA® (r/r) FLT3+ TIBSOVO ® IDH1+ IDHIFA® IDH2+ Targets ~8% of patients Targets ~
Slide 14: SY-2101: Novel oral form of arsenic trioxide
SY-2101 Novel oral form of arsenic trioxide
Slide 15: Value of SY-2101
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-l
Slide 16: Clear development path in front-line APL
Clear development path in front-line APL Dose confirmation study evaluating PK and food effect using Cmax and AUC, and tolerability to identify optimal dose for Phase 3 trial FDA feedback from November 2021 supports: Molecular CR as primary endpoint compared to historic data for accelerated approval
Slide 17: SY-2101 opportunity to reduce treatment burden
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 accou
Slide 18: SY-5609: Highly selective and potent oral CDK7 inhibitor
SY-5609 Highly selective and potent oral CDK7 inhibitor
Slide 19: 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 potency1 1Marineau 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
Slide 20: Tolerability optimized with 7d on/7d off dosing
Tolerability was optimized with 7d on/7d off dosing schedule Phase 1 dose escalation study: Favorable tolerability profile with predominantly low-grade AEs Data presented at ESMO 2021; data cutoff July 6, 2021 Manageable safety profile with majority of AEs low-grade and reversible Low rate of discon
Slide 21: Clinical activity in heavily pretreated patients
Clinical activity seen in heavily pretreated patients; strongest in PDAC, Rb-altered and KRAS-mutant cancers Data presented at ESMO 2021 1Internal company data Highest rates of activity seen in pancreatic cancer patients and Rb-altered tumor cohort1 *Rb-altered patients had tumor types other than br
Slide 22: Exploring SY-5609 in three distinct approaches
Exploring SY-5609 in three distinct approaches based on mechanistic rationale, preclinical data and clinical signals Pancreatic Cancer KRAS mutations are ubiquitous and powerful activators of cell signaling and transcriptional programs Compelling preclinical data and synergy with gemcitabine Single
Slide 23: Expansion cohort in relapsed pancreatic patients
Ongoing expansion cohort in relapsed pancreatic patients provides opportunity to address a high unmet need Expansion ~ 25 patients Endpoints Measures of anti-tumor activity, including DCR and PFS, as well as safety and tolerability Safety lead-in Doublet with gemcitabine Triplet with gemcitabine and
Slide 24: Preclinical data support SY-5609 in BRAF-mutant CRC
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
Slide 25: Planned Phase 1 study of SY-5609 in R/R hematologic malignancies
Leveraging expertise in hematology with planned Phase 1 study of SY-5609 in R/R hematologic malignancies Internal company data B cell lymphomas have multiple oncogenic transcriptional, epigenetic, and cell cycle control drivers. AML associated with alterations in the mitochondrial apoptosis pathway
Slide 26: Gene Control Discovery Engine
Gene Control Discovery Engine
Slide 27: 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 28: Partnered and oncology discovery programs
PARTNERED PROGRAMS Program Target Development Drug Discovery IND-enabling Commercial Rights Sickle cell disease & beta thalassemia Myeloproliferative neoplasms Robust early-stage oncology pipeline to fuel long-term growth ONCOLOGY Program Target Development Drug Discovery IND-enabling Commercial Rig
Slide 29: Multiple value-driving milestones
Multiple value-driving milestones 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 Safety lead-in data from SELECT-AML-1 trial 2H 2022 PK and safety data Mid-2022 Initiate Phase 3 trial 1Q 2023 Data fro
Slide 30: Rapidly advancing toward our vision
Rapidly advancing toward our vision 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 Advancing in late-stage development Capital to fund planned operations in
Slide 31: Appendix
Appendix SYR":S
Slide 32: Preclinical data support SY-5609 in relapsed pancreatic cancer
Preclinical data support SY-5609 in relapsed pancreatic cancer patients in combination with chemotherapy SY-5609 potentiated activity of gemcitibine in pancreatic cancer model using 7d on/7d off regimen Vehicle SY-5609: 3mg/kg, P.O., QD 7/7 Gemcitabine: 50mg/kg, I.P., BIW Combination: Same doses and
Slide 33: SYR2:S
SYR2:S
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