Syros Pharmaceuticals, Inc. · OTC:SYRS
Syros Pharmaceuticals — Investor Presentation (June 2022)
31 slides from Syros Pharmaceuticals's investor presentation, Jun 7, 2022
Slide 1: An Expression Makes a World of Difference
An Expression Makes a World of Difference June 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 and 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: Multiple value-driving milestones
Multiple value-driving milestones Development candidate named from CDK12 program 2H 2022 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 2
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 RAR agonist
Tamibarotene Selective oral RAR agonist
Slide 7: Value of Tamibarotene
Value of Tamibarotene Selective and potent RAR agonist; ~50% of MDS patients and ~30% of AML 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 nov
Slide 8: High CR rates and durability 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 RARA-positive 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: Product candidate targets ~50% of HR-MDS patients
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 RARA-positive HR-MDS patients Physicians are familiar with companion diagnostics to determine opt
Slide 12: Ongoing 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 pati
Slide 13: Tamibarotene targets RARA-positive 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 two distinct approaches
Exploring SY-5609 in two 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 ag
Slide 23: Ongoing safety lead-in in relapsed pancreatic patients
Ongoing safety lead-in of the SY-5609 trial 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
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: Gene Control Discovery Engine
Gene Control Discovery Engine
Slide 26: 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 27: Partnered programs and early oncology pipeline
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 28: 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 29: Appendix
Appendix SYR":S
Slide 30: 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 31: SYR2:S
SYR2:S
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