Zentalis Pharmaceuticals, Inc. · NASDAQ:ZNTL
Zentalis Pharmaceuticals — Technical Presentation (2022)
19 slides from Zentalis Pharmaceuticals's technical presentation, 2022
Slide 1: Safety and clinical activity of single-agent ZN-c3 in uterine serous carcinoma
Safety and clinical activity of single-agent ZN-c3, an oral Wee1 inhibitor, in a Phase 1 trial in subjects with recurrent or advanced uterine serous carcinoma (USC) F. Meric-Bernstam1, P. Chalasani2, H. Mamdani3, C. Zheng4, M. Viana4, R. Lambersky4, P. Pultar4, A. Tolcher5 1MD Anderson Cancer Center
Slide 2: Disclosure Information
Disclosure Information Funda Meric-Bernstam, MD I have the following relevant financial relationships to disclose: Consultant for: AbbVie, Aduro Bio-Tech Inc., Alkermes, AstraZeneca, DebioPharm, eFFECTOR Therapeutics, F. Hoffman-La Roche Ltd., Genentech Inc. IBM Watson, Infinity Pharmaceuticals, Jac
Slide 3: ZN-c3 Mechanism of Action
ZN-c3 Mechanism of Action ZN-c3 is a selective and orally bioavailable small molecule Wee1 inhibitor.1 Wee1 is a crucial component of the G2/M cell cycle checkpoint that prevents cells from entering mitosis and allow repair of DNA damage before cell cycle progression.2-4 Inactive Figure 15 P P P
Slide 4: Uterine Serous Carcinoma
Uterine Serous Carcinoma Endometrial cancer is the most common gynecologic cancer in the United States1 USC is an aggressive histologic type of endometrial cancer, accounting for 10% endometrial cancers but up to 40% of endometrial cancer deaths2 Treatment options for USC include carboplatin a
Slide 5: ZN-c3-001 Study Schema and Endpoints
ZN-c3-001 Study Schema and Endpoints Dose Escalation Dose Expansion MTD/RP2D Dose escalation of ZN-c3 QD plus USC (N = ~40) Subjects with 1-2 additional dosing schedules solid tumors (N = ~70) Biomarkers of Interest (N = ~20) As of January 21, 2022, a total of 80 subjects were enrolled across all
Slide 6: Key Eligibility Criteria: USC Cohort
Key Eligibility Criteria: USC Cohort Histologically confirmed recurrent or persistent USC • At least 10% serous component for mixed histology tumors • Carcinosarcomas excluded Measurable disease per RECIST version 1.1 Prior lines • At least one prior platinum-based chemotherapy for advanced or
Slide 7: Patient Characteristics: USC Cohort
Patient Characteristics: USC Cohort Baseline Characteristic N = 14 Age in years, median (range) 65 (55-72) Race, n (%) White 8 (57.1) For USC, there were Black or African American 5 (35.7) 14 subjects who received Asian 1 (7.1) ZN-c3 at doses ≥ 300 mg QD ECOG Performance Status, n (%) Median dur
Slide 8: All AEs and Treatment-Related AEs for ZN-c3 at 300 mg
All AEs and Treatment-Related AEs for ZN-c3 at 300 mg (≥3 events) all tumors Nausea 78.1 3.1 3.1 71.9 Fatigue 62.5 18.8 18.8 53.1 Diarrhea 56.3 6.3 6.3 46.9 Vomiting 50.0 46.9 Dose modifications Decreased appetite 46.9 6.3 6.3 31.3 Constipation 28.1 3.1 3.1 6.3 Dose reductions, n (%) Edema periphera
Slide 9: Clinical Activity: Response Rate
Clinical Activity: Response Rate N = 11† Best Overall Response n (%) Complete Response (unconfirmed)* 1 (9.1) 100 80 Best Response: uCR PR SD PD Percentage change from baseline (%) Partial Response (confirmed) 2 (18.2) 60 Stable Disease 7 (63.6) 40 ≥ 12 weeks 4 (36.3) 20 PD 4.3% 2.9% ‡ ‡ ‡ ‡ ‡ + ‡ +
Slide 10: Summary of Clinical Activity
Summary of Clinical Activity 40 300 mg/day QD Progressive Disease Percentage change from baseline (%) 300 mg/day QD 20 350 mg/day QD 0 300 mg/day QD 300 mg/day QD Overall Response at Each Assessment -20 Subjects CR 300 mg/day QD PR Partial Response 300 mg/day QD SD -40 PD 300 mg/day QD Best Overall
Slide 11: Responder #1: Overall Summary
Responder #1: Overall Summary 72-year-old, White female, stage IV USC, metastases to peritoneum and lymph node, ECOG PS 1 2 prior lines of therapy in the advanced/metastatic setting ZN-c3 starting dose: 350 mg QD in December 2020 • The subject remained on the study drug for 199 days until radi
Slide 12: Responder #1: Baseline and Follow-up Abdominal Imaging
Responder #1: Baseline and Follow-up Abdominal Imaging Baseline: November 2020 2nd restaging: April 2021
Slide 13: Responder #2: Overall Summary
Responder #2: Overall Summary 69-year-old, African American female, Stage IV USC, metastases to lymph node and lung, ECOG PS 0 4 prior lines of therapy in the advanced/metastatic setting, including prior use of pembrolizumab plus lenvatinib ZN-c3 starting dose: 300 mg QD in January 2021 • The
Slide 14: Responder #2: Baseline and Follow-up Peritoneum Imaging
Responder #2: Baseline and Target #1 Post Follow-up Peritoneum Imaging B B A A A: 11.8 mm B: 11.0 mm A: 19.9 mm B: 16.4 mm Baseline: January 2021 1st restaging: March 2021
Slide 15: Responder #3: Overall Summary
Responder #3: Overall Summary 60-year-old, White female, Stage IV USC, metastases to peritoneum, ECOG PS 1 2 prior lines of therapy in the advanced/metastatic setting, including prior use of pembrolizumab plus lenvatinib ZN-c3 starting dose: 300 mg QD in April 2021 • The subject remained on th
Slide 16: Responder #3: Baseline and Follow-up Peritoneum Imaging
Responder #3: Baseline and Follow-up Peritoneum Imaging Baseline: April 2021 5th restaging: November 2021
Slide 17: Responder #3: Baseline and Follow-up Peritoneum Imaging
Responder #3: Baseline and Follow-up Peritoneum Imaging Baseline: April 2021 5th restaging: November 2021
Slide 18: Conclusions
Conclusions The dose expansion study in USC subjects is still enrolling at both 200 mg and 300 mg QD dose levels Genomic data currently being analyzed ZN-c3 appears to be safe and well-tolerated as a single agent and demonstrated clinical activity in subjects with recurrent or advanced USC • M
Slide 19: Acknowledgements
Acknowledgements Patients and caregivers Study investigators and research staff at: • MD Anderson Cancer Center • NEXT Oncology • University of Arizona Cancer Center • Karmanos Cancer Institute • Community Health Network Cancer Center North Zentalis Pharmaceuticals
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