Syros Pharmaceuticals, Inc. · OTC:SYRS
Syros Pharmaceuticals — Corporate Update (October 2019)
17 slides from Syros Pharmaceuticals's corporate update, Oct 17, 2019
Slide 1: An Expression Makes a World of Difference: CDK7 Portfolio Update
An Expression Makes a World of Difference CDK7 Portfolio Update October 17, 2019 Exhibit 99.2
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: Update on our selective CDK7 inhibitor portfolio
Update on our selective CDK7 inhibitor portfolio Portfolio decision to prioritize SY-5609 and discontinue further development of SY-1365 based on a combination of factors, including: Superior preclinical profile of SY-5609, with best-in-class potential in emerging landscape of oral CDK7 inhibitors I
Slide 4: Selective CDK7 inhibition is a potentially transformative targeted approach
Selective CDK7 inhibition is a potentially transformative targeted approach for difficult-to-treat cancers Apoptosis Selectively inhibiting CDK7 has been shown preclinically to decrease expression of oncogenic transcription factors and anti-apoptotic proteins Selectively inhibiting CDK7 is thought t
Slide 5: Phase 1 clinical trial of SY-1365
Phase 1 clinical trial of SY-1365 Relapsed ovarian cancer, 3+ prior lines Single agent Relapsed ovarian cancer, 1+ prior lines (platinum sensitive) Combination with carboplatin Relapsed clear cell ovarian cancer Single agent Solid tumors accessible for biopsy Single agent HR+ metastatic breast cance
Slide 6: Overview of single-agent safety data from dose escalation and expansion
Overview of single-agent safety data from dose escalation and expansion Majority of AEs were low-grade and reversible Most frequent AEs occurred on the day of infusion and are thought to be related to IV administration These peri-infusional AEs contributed to early discontinuations Lengthening infus
Slide 7: SY-1365 overview of clinical response in expansion portion of Phase 1 trial
SY-1365 overview of clinical response in expansion portion of Phase 1 trial Patients Treated N Response-Evaluable Population N Best Response N (%) Single Agent 53 31 (HGSOC 13; OCC 1; Biopsy 17) Stable Disease: 13 (42%) Combination 15 11 (Carboplatin 8; Fulvestrant 3) Stable Disease: 7 (64%) Majorit
Slide 8: Apoptosis observed in tumor tissue in patients treated with SY-1365
Apoptosis observed in tumor tissue in patients treated with SY-1365 Increases were observed in patients enrolled at doses of 53 mg/m2 and higher, with the highest increases observed in both patients enrolled at 80 mg/m2 One of the two patients enrolled at 80 mg/m2 is the previously reported durable
Slide 9: SY-1365 summary
SY-1365 summary Proof-of-mechanism established with early evidence of clinical activity Majority of AEs thought to be related to IV administration Based on preclinical and clinical data, we believe that: Sustained CDK7 target coverage is needed to enhance clinical activity Achieving sustained target
Slide 10: SY-5609 is a superior development candidate, with best-in-class potential
SY-5609 is a superior development candidate, with best-in-class potential SY-1365 SY-5609 First-in-class ü Convenience ü Potency ü Selectivity ü Dosing flexibility ü Preclinical anti-tumor activity ü
Slide 11: SY-5609: A highly selective and potent non-covalent oral CDK7 inhibitor
SY-5609: A highly selective and potent non-covalent oral CDK7 inhibitor Only 4 of 485 kinases inhibited at ≥90% at 1uM 13,000- to 49,000-fold more selective for CDK7 over CDK2, CDK9 and CDK12 SY-5609 SY-1365 CDK7 potency Kd = 0.059 nM KI = 20 nM CDK12 (fold) CDK2 (fold) CDK9 (fold) 13,000x 49,000x 1
Slide 12: SY-5609 shows tumor growth inhibition, including regressions, below MTD
SY-5609 shows tumor growth inhibition, including regressions, below MTD Regressions observed at 5-fold below MTD of ≥10 mg/kg QD Triple negative breast cancer model Dashed lines represent end of treatment Days Post Treatment Initiation
Slide 13: SY-5609 shows robust anti-tumor activity in multiple PDX models
SY-5609 shows robust anti-tumor activity, including complete regressions, in multiple PDX models Triple-negative breast cancer model High-grade serous ovarian cancer model Small-cell lung cancer model Dashed lines represent end of treatment Vehicle 10mpk QD 5mpk BID Days Post Treatment Initiation Ve
Slide 14: SY-5609 shows greater anti-tumor activity than SY-1365 in head-to-head study
SY-5609 shows greater anti-tumor activity than SY-5609 in head-to-head preclinical study Pancreatic cancer PDX model SY-5609 induces 100% tumor growth inhibition at doses below MTD By comparison, SY-1365 induces modest tumor growth inhibition at MTD Vehicle SY-1365 40 mg/kg BIW, IV SY-5609 6 mg/kg Q
Slide 15: 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 16: Key takeaways
Key takeaways Selective CDK7 inhibition is a potentially transformative targeted approach for difficult-to-treat cancers SY-1365 demonstrated early evidence of clinical activity and we believe more sustained CDK7 target coverage is needed to improve treatment outcomes SY-5609 is a superior developme
Slide 17: Syros
SYR=S
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