Slide 1: SY-5609 Phase 1 Dose-Escalation Data and Next Steps
SY-5609 Phase 1 Dose-Escalation Data and Next Steps September 20, 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: Here's what you will take away from today
Here’s what you will take away from today Identified an optimal dosing regimen for further development of SY-5609, based on tolerability, PD and clinical activity that we believe is ideally suited for various combinations SY-5609 demonstrated single-agent activity, including prolonged stable disease
Slide 4: Accelerating our vision
Accelerating our vision Targeted hematology therapy franchise Gene control discovery engine Selective CDK inhibitor franchise Fully integrated biopharmaceutical company
Slide 5: Advancing a growing clinical-stage pipeline for targeted patient populations
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: SY-5609 Dose-Escalation Data
SY-5609 Dose-Escalation Data David A. Roth, M.D.
Slide 7: Our vision for SY-5609
Our vision for SY-5609 Next Combinations in solid tumors and blood cancers Vision Transformative targeted therapy for difficult-to-treat cancers Now Single-agent POA and optimal regimen for combinations
Slide 8: 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 9: Ongoing Phase 1 dose escalation in patients with select solid tumors
Ongoing Phase 1 dose escalation in patients with select solid tumors Enrolled patients with advanced breast, colorectal, lung, ovarian or pancreatic cancer, as well as other tumor types with Rb pathway alterations Standard 3+3 dose escalation Objectives included safety, tolerability, PK, PD and anti
Slide 10: Baseline Characteristics and Patient Disposition
Baseline Characteristics and Patient Disposition Baseline Characteristics (n=54) Median Age, years (range) 65.5 (44-81) Gender, n (%) Female 34 (63) Median # prior therapies (range) 4 (1-8) ≥ 5 Prior therapies, n (%) 22 (41) Cancer Type, n (%) Breast 2 (3) Colorectal 8 (15) NSCLC 6 (11) Ovarian 8 (1
Slide 11: Tolerability was optimized with 7d on/7d off dosing schedule
Tolerability was optimized with 7d on/7d off dosing schedule AE summary across all doses and schedules Manageable safety profile with majority of AEs low-grade and reversible Majority of AEs were low-grade and reversible Most frequent TEAEs: GI, fatigue, thrombocytopenia, anemia Low rate of disconti
Slide 12: Clinical activity seen in heavily pretreated patients across multiple tumor types
Clinical activity seen in heavily pretreated patients across multiple tumor types 13 of 45 (28.9%) response-evaluable patients achieved stable disease (SD) across doses and schedules Of those, six had tumor regressions of up to 20% SD achieved in daily and intermittent dose cohorts with doses as low
Slide 13: Analysis of clinical activity by tumor type and mutational status
Analysis of clinical activity by tumor type and mutational status supports mechanistic rationale in Rb-altered and KRAS-mutant cancers Highest rates of activity seen in pancreatic cancer patients and Rb-altered tumor cohort **43 patients had ctDNA analysis of KRAS mutations at baseline. *Rb-altered
Slide 14: More than double the rate of clinical activity seen in pancreatic cancer
More than double the rate of clinical activity seen in pancreatic cancer, compared to other tumor types 69-year-old patient with metastatic disease in 3rd relapse No response to prior FOLFIRINOX and Xeloda; relapsed after Gem/nab-Pac chemotherapy just prior to starting on study Remained in SD for 10
Slide 15: PD responses are associated with anti-tumor activity in patients
PD responses are associated with anti-tumor activity in patients; sustained PD activity further supports intermittent dosing In 33 response-evaluable patients with matching single-dose POLR2A PD PBMC data 100% (16/16) of patients in upper 50th percentile of PD response had target lesions that remain
Slide 16: SY-5609 Development Strategy
SY-5609 Development Strategy Kristin Stephens
Slide 17: Three-pronged combination strategy aimed at maximizing potential of SY-5609
Three-pronged combination strategy aimed at maximizing potential of SY-5609 Strong mechanistic rationale + Early clinical activity + Compelling preclinical data + High unmet need + Potential for first-in-indication leadership position Pancreatic cancer in combination with chemo Mantle cell lymphoma
Slide 18: CDK7i disrupts the CDK and transcriptional activity needed to progress through the cell cycle
CDK7i disrupts the CDK and transcriptional activity needed to progress through the cell cycle Altered Rb pathway BRAF and KRAS mutations CDK1 CDK2 Selective CDK7 inhibition attacks two fundamental processes in cancer Cell Cycle Transcription CDK7i MYC MYB MCL1 MCL1 Apoptosis CDK7i has been shown pre
Slide 19: Focusing on cancers driven by transcriptional and cell cycle dependencies
Focusing on cancers driven by transcriptional and cell cycle dependencies KRAS mutations, which are ubiquitous in pancreatic cancer, are powerful activators of cell signaling and transcriptional programs for cell cycle progression Pancreatic cancer Mantle cell lymphoma BRAF-mutant colorectal cancer
Slide 20: Preclinical data support SY-5609 in relapsed pancreatic cancer in combination with chemotherapy
Preclinical data support SY-5609 in relapsed pancreatic cancer patients in combination with chemotherapy SY-5609 potentiates 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 21: Opportunity to address unmet need in pancreatic cancer
Opportunity to address unmet need in pancreatic cancer High unmet need in metastatic pancreatic cancer Commonly diagnosed in advanced stages, with poor prognosis due to lack of effective treatment and rapid disease progression1 Incidence of second-line patients is ~27,500 in US2 Only approved second
Slide 22: Preclinical data support SY-5609 in BRAF-mutant CRC in combination with PDL1 inhibitor
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 CRC data pr
Slide 23: Preclinical data support SY-5609 in mantle cell lymphoma in combination with BTK inhibitor
Preclinical data support SY-5609 in mantle cell lymphoma in combination with BTK inhibitor SY-5609 is synergistic with BTK inhibitor in MCL cell line in vitro Internal company data Leverages expertise in hematology and supports our growing targeted hematology portfolio Hallmark of MCL is a genetic t
Slide 24: Opportunity to address unmet medical need in relapsed mantle cell lymphoma
Opportunity to address unmet medical in relapsed mantle cell lymphoma High unmet need in mantle cell lymphoma Accounts for 5-10% of all non-Hodgkin lymphomas, with incidence of ~10,000 in US and EU1 Worst prognosis among all lymphomas Despite durable response rates in first-line setting, patients ev
Slide 25: Key takeaways
Key takeaways Identified an optimal dosing regimen for further development of SY-5609, based on tolerability, PD and clinical activity that we believe is ideally suited for various combinations SY-5609 demonstrated single-agent activity, including prolonged stable disease (SD), tumor shrinkage and t
Slide 26: Multiple expected value-driving milestones and strong cash position
Multiple expected value-driving milestones and strong cash position SY-5609 SY-2101 Tamibarotene w/ aza Tamibarotene w/ ven+aza Initiate SELECT-MDS-1 trial in ND HR-MDS Potential NDA filing in ND HR-MDS 2024 Initiate SELECT-AML-1 trial in ND unfit AML Initial data from SELECT-AML-1 trial in ND unfit
Slide 27: SY R=S
SY R=S