Syros Pharmaceuticals, Inc. · OTC:SYRS
Syros Pharmaceuticals — Investor Presentation (December 2019)
27 slides from Syros Pharmaceuticals's investor presentation, Dec 2, 2019
Slide 1: An Expression Makes a World of Difference
An Expression Makes a World of Difference December 2, 2019 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: Deep gene control pipeline
Program Indication Drug Discovery IND- Enabling Early Clinical Mid- Clinical Pivotal SY-1425 (RARα agonist) Newly diagnosed unfit AML R/R AML SY-5609 (Oral CDK7 inhibitor) Cancer CDK12/13 inhibitor Cancer Macrophage target Cancer Monogenic disease Sickle cell disease Deep gene control pipeline SY-14
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 with 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: SY-1425 with azacitidine generally well-tolerated
SY-1425 in combination with azacitidine 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
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: Phase 2 trial of SY-1425 with azacitidine in RARA-positive AML
Ongoing Phase 2 trial evaluating SY-1425 in combination with azacitidine in RARA-positive AML, with opportunity for rapid proof-of-concept Enrollment complete in newly diagnosed unfit cohorts Potential proof-of-concept data in relapsed or refractory AML expected in 2020 Phase 2 clinical trial design
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 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: 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: SY-5609 shows tumor growth inhibition below MTD in preclinical models
SY-5609 shows tumor growth inhibition, including regressions, 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/
Slide 17: SY-5609 robust anti-tumor activity in multiple solid tumor models
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 SY-5609 shows robust anti-tumor activity, including complete regressions, in preclinical models of multiple solid tum
Slide 18: SY-5609 responses in treatment-resistant ER+ breast cancer models
SY-5609 induces 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 inhib
Slide 19: Responses associated with Rb alterations in preclinical studies
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 On track to complete IND-enabling studies by year-end Dose escalation will enroll patients with select solid tumors Focusing on patient populations we believe are enriched for response, including: Breast Lung Ovarian Solid tumors of
Slide 21: Robust early-stage pipeline to fuel long-term growth
Program Target Development Drug Discovery IND-Enabling Cancer CDK12/13 inhibitor Macrophage target Cancer Monogenic Disease Sickle cell disease Other monogenic diseases Partnered (Incyte) Myeloproliferative neoplasms Robust early-stage pipeline to fuel long-term growth
Slide 22: Monogenic disease: alter expression of a single gene
Monogenic disease: Alter expression of a single gene for therapeutic benefit SCD caused by mutated adult globin gene Fetal globin gene typically turned off at birth In some SCD patients, the fetal globin gene remains on and is associated with milder disease Sickle cell disease (SCD) Clinical and gen
Slide 23: Milestones expected in 2019 and 2020
Milestones expected in 2019 and 2020 Q4 2019 2020 SY-1425 SY-5609 Discovery Completed enrollment in ND unfit AML Updated data in ND unfit AML Potential POC in R/R AML Complete IND-enabling studies Initiate Phase 1 oncology trial in Q1 2020 SABCS presentation on metastasis in TNBC ASH oral presentati
Slide 24: 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 to key milestones Advanc
Slide 25: SYROS
SYR=S
Slide 26: SY-1365 infusion-associated adverse events and target engagement
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 27: RARA is not a prognostic biomarker in AML patients
RARA is not a prognostic biomarker in AML patients 27 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, NE
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