Syros Pharmaceuticals, Inc. · OTC:SYRS
Syros Pharmaceuticals — Investor Presentation (January 2020)
29 slides from Syros Pharmaceuticals's investor presentation, Jan 13, 2020
Slide 1: An Expression Makes a World of Difference
An Expression Makes a World of Difference January 13, 2020 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: Our Vision
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
Slide 4: 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 5: Pipeline programs by indication and development stage
Program Indication Drug Discovery IND- Enabling Early Clinical Mid- Clinical Pivotal Commercial Rights SY-1425 (RARα agonist) Newly diagnosed unfit AML R/R AML SY-5609 (Oral CDK7 inhibitor) Cancer CDK12/13 inhibitor Cancer Macrophage target Cancer/immune modulation LRF & NuRD modulators Sickle cell
Slide 6: Our vision for SY-1425 in RARA-positive patients
Our vision for SY-1425 in RARA-positive patients Now Combination with aza Opportunity for rapid proof-of concept Next Registration studies for aza combo Additional combinations and RARA-positive populations Vision Foundation of care for all RARA-positive patients
Slide 7: SY-1425 binds to RARα and activates differentiation genes
1425 SY-1425 binds to RARα and activates differentiation genes Novel combination approach for RARA-positive AML patients RARa Aza cross links to DNA SY-1425 enhances apoptosis preclinically Apoptosis DNA damage Gene control platform identifies novel patient subset SY-1425 shows synergy with a range
Slide 8: SY-1425 plus azacitidine shows high complete response rates in RARA-positive AML
Best Response CR CRm CRm MR PRi PRi CRc CRm CRc CRi CRc PRi MR SY-1425 in combination with azacitidine shows high complete response rates, deep CRs and rapid onset of action in RARA-positive AML patients 0 50 100 150 200 250 300 350 400 450 500 550 86% of CRs were deep molecular or cytogenetic CRs D
Slide 9: Combination has been generally well-tolerated
Combination has been generally well-tolerated with no evidence of increased toxicities AEs consistent with single-agent SY-1425 or azacitidine in AML Rates of myelosuppression comparable to reports of single-agent azacitidine Majority of non-hematologic AEs were low grade Preferred Term All Grades N
Slide 10: RARA as the optimal biomarker for patient selection
Deep CRs and high CR rates in RARA-positive patients support RARA as the optimal biomarker for patient selection 27% CR/CRi rate in RARA-negative consistent with single-agent azacitidine1 RARA is not a prognostic biomarker in AML, based on analyses of TCGA, BeatAML and company data RARA does not app
Slide 11: Significant need for well-tolerated oral therapies in AML
Significant need for well-tolerated oral therapies that improve outcomes and quality of life Fast-growing AML market is projected to be ~ $1 billion this year R/R AML Clinical trials are preferred treatment strategy Recently approved therapies target limited patient subsets, with composite CR rates
Slide 12: Ongoing Phase 2 trial with opportunity for rapid proof-of-concept
Ongoing Phase 2 trial with opportunity for rapid proof-of-concept Potential proof-of-concept data in relapsed or refractory AML expected in Q4 2020 Enrollment complete in newly diagnosed unfit cohorts; mature data expected in Q4 2020 Phase 2 clinical trial design (25-patient cohorts) Biomarker-posit
Slide 13: Our vision for selective CDK7 inhibition
Our vision for selective CDK7 inhibition in difficult-to-treat cancers Now Advancing SY-5609 into clinical development Next Initial data from Phase 1 Explore combinations Vision Transformative targeted approach for difficult-to-treat solid tumors and blood cancers
Slide 14: Selective CDK7 inhibition attacks two fundamental processes in cancer
Selective CDK7 inhibition attacks two fundamental processes in cancer Apoptosis Selectively inhibiting CDK7 has been shown preclinically to decrease expression of oncogenic transcription factors and anti-apoptotic proteins Selectively inhibiting CDK7 is thought to interfere with cancer-driving adapt
Slide 15: SY-5609: A highly selective oral CDK7 inhibitor
SY-5609: A highly selective oral CDK7 inhibitor with best-in-class potential 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 Data presented in October 201
Slide 16: Tumor growth inhibition observed below MTD in preclinical models
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 mg/kg BID
Slide 17: Robust anti-tumor activity in preclinical models of multiple solid tumors
Days 0 10 20 30 40 0 100 200 300 400 Tumor Volume (mm3) 0 10 20 30 Days 40 0 500 1000 1500 2000 Tumor Volume (mm3) High-grade serous ovarian cancer model Small-cell lung cancer model Robust anti-tumor activity, including complete regressions, in preclinical models of multiple solid tumors Colorectal
Slide 18: Robust responses in treatment-resistant ER+ breast cancer models
Robust responses in preclinical treatment-resistant ER+ 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 Data presented in October 2019 at EORTC-NCI-AACR Conference CDK4/6 inhibitor resistant m
Slide 19: Deeper responses associated with Rb alterations
Deeper and more sustained responses associated with Rb alterations in preclinical studies of breast, lung and ovarian cancers Data presented in October 2019 at EORTC-NCI-AACR Conference 29% of basal breast cancer patients1 ~1/3 of HR+ breast cancer patients post CDK4/6 inhibitors2 75-90% of small ce
Slide 20: Expect to initiate Phase 1 trial in select solid tumors in Q1 2020
Expect to initiate Phase 1 trial in select solid tumors in Q1 2020 Focused on breast, lung, colorectal and ovarian cancers and any solid tumors with Rb alterations PK/PD guided dose escalation Initial safety, tolerability and PK/PD data expected in Q4 2020 Additional dose escalation data, including
Slide 21: Robust early-stage pipeline to fuel long-term growth
Therapeutic Area Program Target Development Drug Discovery IND-Enabling Commercial Rights Cancer CDK12/13 inhibitor Target 1 Target 2 Target 3 Myeloproliferative neoplasms Cancer/Immune modulation Macrophage target Monogenic Disease Sickle cell disease & beta thalassemia Myotonic dystrophy type 1 Ro
Slide 22: Oral medicine to turn on fetal globin gene for sickle cell disease
Discovering an oral medicine to turn on fetal globin gene with aim of providing a functional cure for 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
Slide 23: Collaboration with Global Blood Therapeutics
Expanding our efforts in sickle cell disease and beta thalassemia through collaboration with Global Blood Therapeutics Option to obtain exclusive worldwide license to products resulting from the collaboration Responsible for clinical development, manufacturing and commercialization $20 million upfro
Slide 24: Milestones expected in 2020 and 2021
Milestones expected in 2020 and 2021 SY-1425 SY-5609 Discovery Potential POC in relapsed or refractory AML Q4 2020 Mature data in newly diagnosed unfit AML Q4 2020 Initiate Phase 1 trial Q1 2020 Initial safety, tolerability and PK/PD data Q4 2020 Additional dose escalation data, including clinical a
Slide 25: Rapidly advancing toward our vision
Rapidly advancing toward our vision Progressing to pivotal development Advancing multiple programs in clinic Preparing for commercial launch Continued investment in discovery Fully integrated company with medicines that provide a profound benefit for patients Driving SY-1425 and SY-5609 to key clini
Slide 26: Appendix
Appendix
Slide 27: Peri-infusional AEs associated with peak SY-1365 concentrations
1H2H1H 2H 53 mg/m2 64 mg/m2 Peri-infusional AEs in Phase 1 trial were associated with peak blood SY-1365 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 A
Slide 28: 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 29: Syros
SYR=S
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