Six sponsored studies with potentially first-in-class Wee1 inhibitor, ZN-c3, ongoing and continuing dose optimization work, as drug continues to show improved tolerability in initial safety data from monotherapy Phase 2
Identified Cyclin E driven high-grade serous ovarian cancer patients as initial expansion population for ZN-c3 biomarker monotherapy trial
Announced first ZN-c3 clinical development collaboration with Pfizer in BRAF mutant mCRC; Expanded ZN-c3 clinical development collaboration with GSK in PARP resistant ovarian cancer
Declared BCL-xL protein degrader candidate and initiated IND-enabling studies; Molecule has broad potential across multiple tumor types and in combination
Strengthened Board and management team with appointments of Chief Medical Officer, Chief Scientific Officer and Chief Translational Officer
“During the third quarter, we made tremendous progress advancing our clinical strategy and corporate capabilities. We have established a three-pronged development plan for ZN-c3, our potentially first-in-class Wee1 inhibitor—investigation as a monotherapy, in combination with chemotherapy, and in combination with targeted therapies,” said
Wee1 Inhibitor (ZN-c3) Program Highlights
- Monotherapy in
USC safety and enrollment update: As of a data cutoff onSeptember 14, 2022 , a total of 43 patients were enrolled and dosed in the Phase 2 monotherapy uterine serous carcinoma (USC) trial. ZN-c3 was well tolerated and the safety profile was similar or improved relative to previously disclosed data, exhibiting a better hematological and gastrointestinal tolerability profile. TheU.S. Food and Drug Administration has granted Fast Track designation to ZN-c3 in this setting. - Cyclin E biomarker strategy in high-grade serous ovarian cancer: The Company announced that Cyclin E overexpression and/or amplification in high-grade serous ovarian cancer will become the focus of its ongoing Phase 1/2 clinical study examining biomarker-driven enrichment strategies for ZN-c3. Cyclin E overexpression acts at the G1-S checkpoint by driving premature entry into S-phase resulting in replicative stress and significantly increases sensitivity to ZN-c3. The Company has generated preclinical data showing that Cyclin E overexpression sensitizes cancer cells to the anti-tumor effects of ZN-c3 as well as preliminary retrospective clinical data that Cyclin E protein levels may be associated with clinical benefit from ZN-c3. The Company plans to present the preclinical data in the first half of 2023. The two new cohorts of patients will be given monotherapy, which will potentially generate meaningful data sets in patients with Cyclin E gene amplification and patients with Cyclin E protein overexpression independent of gene amplification.
- Dose optimization: The Company highlighted that it continues to optimize dosing across the ZN-c3 clinical portfolio to maximize exposure, improve normal tissue tolerability and enable maximum probability of success. The Company anticipates that the Phase 2
USC trial dose will be modified based on these ongoing dose optimization studies and that, as a result, the timeline of theUSC study will be extended. The Company anticipates providing an update on ZN-c3 dosing in the first half of 2023, including expected program timelines and potential paths to registration. - Pfizer collaboration in mCRC: Zentalis and Pfizer are collaborating on a Phase 1/2 dose escalation study of ZN-c3 in combination with encorafenib and cetuximab (BEACON regimen) in BRAF V600E-mutated metastatic colorectal cancer (mCRC) patients. In preclinical studies, Wee1 inhibition has shown synergy with many targeted agents in mutationally driven cancers, and the addition of ZN-c3 to the BEACON regimen enhanced anti-tumor activity in a cell-line-derived xenograft model. Additional information on this clinical development collaboration is available here.
- GSK collaboration in ovarian cancer: Zentalis and GSK are expanding their ongoing collaboration looking at the clinical synergy of ZN-c3 and niraparib in PARP resistant ovarian cancer. The Phase 1/2 dose escalation study, currently enrolling with concurrent dosing of the two drugs, will be expanded to include a cohort that will be given ZN-c3 and niraparib on a dose escalating, alternating schedule of one week of ZN-c3 followed by one week of niraparib.
- Chemotherapy combination in platinum-resistant ovarian cancer: The Company continues to enroll its dose escalation trial of standard chemotherapy (paclitaxel, gemcitabine, and carboplatin) in platinum-resistant ovarian cancer.
- Chemotherapy combination in osteosarcoma: The Company will be presenting initial data from its Phase 1/2 combination trial of ZN-c3 and chemotherapy in osteosarcoma in a poster session at the upcoming
Connective Tissue Oncology Society (CTOS) 2022 Annual Meeting, being heldNovember 16-19 inVancouver . Details for the CTOS poster presentation are as follows:- Title: Preliminary Data from a Phase 1 Dose Escalation Study of ZN-c3 Plus Gemcitabine in Relapsed/Refractory Osteosarcoma (NCT04833582)
- Session: Medical & Pediatric Oncology and Trials
- Date/Time:
November 17, 2022 from5:00pm to 7:00pm ET - Presenter: Viswatej Avutu, MD, Assistant Attending Physician at
Memorial Sloan Kettering Cancer Center
- Dana-Farber combination study in platinum-resistant pancreatic cancer: Zentalis announced an investigator-initiated trial with
Dana-Farber Cancer Institute , funded byStand Up To Cancer and theLustgarten Foundation , to explore the combination of ZN-c3 with gemcitabine in platinum-resistant advanced pancreatic adenocarcinoma.James Cleary , MD, PhD, Director, Clinical Research,Division of Gastrointestinal Oncology at theDana-Farber Cancer Institute , andBrandon Huffman , MD, Adult Medical Oncology Fellow at theDana-Farber Cancer Institute , will be running this trial. “We are pleased to announce this important trial which builds on the growing body of clinical evidence supporting the use of ZN-c3 across a range of tumor types,” saidDr. Cleary . “Pancreatic cancer continues to be an area of high unmet patient need, and we look forward to understanding the potential role of ZN-c3 in helping these patients.”
BCL-2 Inhibitor (ZN-d5) Update
- Monotherapy dose optimization continues in NHL and amyloidosis: Dosing with food is ongoing in patients in non-Hodgkin lymphoma (NHL) and amyloidosis, and the combination study of ZN-d5 and ZN-c3 in acute myeloid leukemia (AML) is scheduled to initiate in the fourth quarter of 2022.
BCL-xL Degrader Update
- Declared candidate and initiated IND-enabling studies: BCL-xL degrader candidate demonstrates potent anti-cancer activity in several preclinical models and has the potential to have platelet sparing benefits over clinical-stage BCL-xL targeted inhibitors.
Corporate Highlights
- In September, Zentalis appointed
Jan Skvarka , PhD, MBA, to its Board of Directors.Dr. Skvarka is an accomplished biopharmaceutical executive bringing over three decades of extensive operational, strategic and financial expertise to Zentalis.Dr. Skvarka was formerly Chief Executive Officer ofTrillium Therapeutics, Inc. , which was acquired by Pfizer under his leadership. - In October, the Company promoted co-founder
Kevin Bunker , PhD, to Chief Scientific Officer. In this new role,Dr. Bunker will focus on leading Research and Development and advancing the preclinical pipeline with the Company’s Integrated Discovery Engine. - In October, Zentalis appointed
Carrie Brownstein , MD, as Chief Medical Officer.Dr. Brownstein , a leading oncologist and hematologist, joins Zentalis with over two decades of medical and biopharmaceutical experience, successfully executing clinical program strategies across all phases of product development. - In October, the Company appointed
Mark Lackner , PhD, as Chief Translational Officer, Head of Biomarker Strategy.Dr. Lackner , a recognized and respected cancer biologist, joins Zentalis with over two decades of oncology-focused drug development expertise, including significant experience in biomarker discovery and clinical biomarker strategies.
Third Quarter 2022 Financial Results
- Cash and Marketable Securities Position: As of
September 30, 2022 , Zentalis had cash, cash equivalents and marketable securities of$421.7 million . The Company believes that its existing cash, cash equivalents and marketable securities as ofSeptember 30, 2022 will be sufficient to fund its operating expenses and capital expenditure requirements into the first quarter of 2025. - Research and Development Expenses: Research and development (R&D) expenses for the three months ended
September 30, 2022 were$42.2 million , compared to$54.0 million for the three months endedSeptember 30, 2021 . The decrease of$11.8 million was primarily due to non-recurring R&D impairments and licensing milestones of$8.8 million and$5.0 million , respectively, recorded during the three months endedSeptember 30, 2021 . Other decreases in R&D expenses included$4.6 million in decreased manufacturing and collaborative expenses, and$0.3 million of additional reimbursement from Zentera under our cost sharing arrangement. These decreases were offset by increases of$3.4 million ,$3.1 million and$0.4 million of clinical trial related costs, personnel and consulting costs, and overhead allocations, respectively. - General and Administrative Expenses: General and administrative expenses for the three months ended
September 30, 2022 were$12.0 million , compared to$8.9 million during the three months endedSeptember 30, 2021 . This increase of$3.1 million was primarily attributable to an increase in non-cash, stock-based compensation expense of$1.8 million and$0.3 million related to other compensation expense. Increases of$1.9 million ,$0.6 million and$0.5 million were seen in rent and depreciation expense, external consulting expense and legal expense, respectively. These amounts were partially offset by a decrease in permits and fees and allocation of overhead expenditures to R&D of$1.6 million and$0.4 million , respectively.
About
For more information, please visit www.zentalis.com. Follow Zentalis on Twitter at @ZentalisP and on LinkedIn at www.linkedin.com/company/zentalis-pharmaceuticals.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the
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Investor Contacts:
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Media Contact:
jdeutsch@soleburystrat.com
Condensed Consolidated Statements of Operations | |||||||||||||||
(Unaudited) | |||||||||||||||
(In thousands, except per share amounts) | |||||||||||||||
Three Months Ended | Nine Months Ended | ||||||||||||||
2022 | 2021 | 2022 | 2021 | ||||||||||||
Operating Expenses | |||||||||||||||
Research and development | $ | 42,181 | $ | 53,998 | $ | 132,118 | $ | 137,162 | |||||||
General and administrative | 12,012 | 8,872 | 43,415 | 31,187 | |||||||||||
Total operating expenses | 54,193 | 62,870 | 175,533 | 168,349 | |||||||||||
Operating loss | (54,193 | ) | (62,870 | ) | (175,533 | ) | (168,349 | ) | |||||||
Other Income (Expense) | |||||||||||||||
Investment and other income, net | 1,905 | 99 | 2,755 | 313 | |||||||||||
Gain on deconsolidation of Zentera | — | 51,582 | — | 51,582 | |||||||||||
Net loss before income taxes | (52,288 | ) | (11,189 | ) | (172,778 | ) | (116,454 | ) | |||||||
Income tax expense (benefit) | (159 | ) | (697 | ) | (109 | ) | (456 | ) | |||||||
Loss on equity method investment | 2,371 | — | 9,460 | — | |||||||||||
Net loss | (54,500 | ) | (10,492 | ) | (182,129 | ) | (115,998 | ) | |||||||
Net loss attributable to noncontrolling interests | (99 | ) | (6,301 | ) | (294 | ) | (7,332 | ) | |||||||
Net loss attributable to Zentalis | $ | (54,401 | ) | $ | (4,191 | ) | $ | (181,835 | ) | $ | (108,666 | ) | |||
Net loss per common share outstanding, basic and diluted | $ | (0.96 | ) | $ | (0.09 | ) | $ | (3.56 | ) | $ | (2.59 | ) | |||
Common shares used in computing net loss per share, basic and diluted | 56,807 | 44,609 | 51,098 | 41,918 | |||||||||||
Selected Condensed Consolidated Balance Sheet Data | ||||||
(Unaudited) | ||||||
(In thousands) | ||||||
As of | As of | |||||
2022 | 2021 | |||||
Cash, cash equivalents and marketable securities | $ | 421,726 | $ | 339,887 | ||
Working capital (1) | 379,829 | 306,826 | ||||
Total assets | 529,193 | 454,507 | ||||
Total liabilities | 100,455 | 90,025 | ||||
Total Zentalis equity | $ | 428,738 | $ | 364,482 | ||
(1) The Company defines working capital as current assets less current liabilities. |
Source:
2022 GlobeNewswire, Inc., source