Zentalis Pharmaceuticals Announces First Patient Dosed in the Phase 1/2 Study of ZN-c3 in Combination with Gemcitabine in Patients with Osteosarcoma

Rhea-AI Summary

Zentalis Pharmaceuticals, Inc. (Nasdaq: ZNTL) has initiated a Phase 1/2 trial for ZN-c3, an oral WEE1 inhibitor, in combination with gemcitabine for treating relapsed or refractory osteosarcoma. The trial aims to evaluate clinical safety and efficacy, with initial results expected in the second half of 2022. Zentalis has received orphan drug and rare pediatric disease designations from the FDA for this indication, potentially leading to a priority voucher upon approval. Osteosarcoma, primarily affecting younger patients, has a poor prognosis, highlighting the urgent need for effective therapies.

Positive

• Initiation of a Phase 1/2 trial for ZN-c3, indicating progress in clinical development.
• ZN-c3 received orphan drug and rare pediatric disease designations from the FDA, facilitating regulatory advantages.
• Potential eligibility for a rare pediatric disease priority voucher could enhance market value.

Negative

• Osteosarcoma has a historically poor prognosis, indicating high clinical risk for trial outcomes.
• There is no mention of funding or partnerships to support the clinical trial, raising concerns about resource availability.

Initial results are expected in 2H 2022

NEW YORK and SAN DIEGO, Sept. 13, 2021 (GLOBE NEWSWIRE) -- Zentalis Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage biopharmaceutical company focused on discovering and developing small molecule therapeutics targeting fundamental biological pathways of cancers, today announced that the first patient has been dosed in the Phase 1/2 trial of ZN-c3, the Company’s oral WEE1 inhibitor product candidate, in combination with gemcitabine, a chemotherapy used to treat certain malignant tumors, in pediatric and adult patients with relapsed or refractory osteosarcoma.

“We are thrilled to expand our ZN-c3 program with the initiation of a fourth clinical trial for this candidate, underscoring ZN-c3’s potential versatility across a broad range of solid tumors,” commented Dr. Anthony Sun, Chairman and Chief Executive Officer of Zentalis. “Relapsed or refractory patients with osteosarcoma, a rare type of bone cancer, have an extremely poor prognosis, reinforcing the need for novel treatment regimens to combat this highly aggressive disease. With over 50% of osteosarcomas having a mutation in TP53 – potentially resulting in chemoresistance – we believe that inhibiting the DNA damage response protein WEE1 could enhance the efficacy of gemcitabine in this pre-treated population. We are eager to conduct this seminal study evaluating this combination’s clinical safety and efficacy and look forward to reporting initial results from this trial in the second half of 2022.”

Zentalis recently received orphan drug and rare pediatric disease designations from the U.S. Food and Drug Administration for pediatric osteosarcoma. If ZN-c3 were to obtain approval for the designated indication, it could potentially be eligible for a rare pediatric disease priority voucher upon approval.

The Phase 1/2 trial (ZN-c3-003) is a dose escalation and dose expansion study, evaluating the clinical activity, safety, pharmacodynamics and pharmacokinetics of ZN-c3 in combination with gemcitabine in relapsed or refractory osteosarcoma. The primary efficacy endpoint is event-free survival (EFS) at 18 weeks per RECIST criteria. Secondary endpoints include EFS per RECIST, median overall survival and overall survival at 12 months. More information about the trial is available at www.clinicaltrials.gov: NCT04833582.

About Osteosarcoma

Osteosarcoma, while rare, is the most common type of bone cancer and is often associated with a high degree of malignancy, early metastasis, rapid progression, and poor prognosis. This cancer occurs primarily in children, teens and young adults ranging from 10 to 30 years old. The risk of diagnosis decreases in adulthood, but rises again in older adults usually over the age of 60. Approximately 1,000 new cases of osteosarcoma are diagnosed in the United States each year. Treatment typically includes a combination of surgery and chemotherapy, with chemotherapy administered before and after surgery to help lower the risk of relapse. Even though curative therapy is available for the primary tumor, long-term outcomes for osteosarcoma patients continue to be impacted by metastatic progression. In addition, over 50% of osteosarcomas have a mutation in TP53 which portends a poorer prognosis and implies chemoresistance. As no substantive improvements in long-term outcomes have occurred for more than three decades, there remains an urgent need for improved therapies to prevent or treat metastatic disease.

About ZN-c3

ZN-c3 is a potentially first-in-class and best-in-class oral inhibitor of WEE1 in development for the treatment of advanced solid tumors. The inhibition of WEE1, a DNA damage response protein, aims to generate sufficient DNA damage in cancer cells, causing cell death, thereby preventing tumor growth and potentially causing tumor regression. ZN-c3 has broad potential as a monotherapy and in combination and we are currently evaluating this candidate in several ongoing and planned studies, including two potentially registrational monotherapy trials in USC and a biomarker-driven setting, as well as combination studies such as with chemotherapy in patients with advanced ovarian cancer. We also recently received orphan drug and rare pediatric disease designations from the FDA for pediatric osteosarcoma and have initiated a Phase 1/2 trial in combination with chemotherapy.

About Zentalis Pharmaceuticals

Zentalis Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on discovering and developing small molecule therapeutics targeting fundamental biological pathways of cancers. The Company is developing a broad pipeline of potentially best-in-class oncology candidates, all internally discovered, which include ZN-c3, a WEE1 inhibitor for advanced solid tumors, ZN-c5, an oral selective estrogen receptor degrader (SERD) for ER+/HER2- breast cancer, ZN-d5, a BCL-2 inhibitor for hematologic malignancies, and ZN-e4, an EGFR inhibitor for non-small cell lung carcinoma (NSCLC). Zentalis has licensed ZN-c3, ZN-c5 and ZN-d5 to its joint venture, Zentera Therapeutics, to develop and commercialize these candidates in China. Zentalis has operations in both New York and San Diego.

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 Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding our expectations surrounding the development, potential, safety, efficacy, and regulatory and clinical progress of our product candidates, including without limitation ZN-c3, in the Unites States and globally, potential eligibility of ZN-c3 for a rare pediatric disease priority voucher and plans and timing for the initiation of and the release of data from our clinical trials and our ability to meet other key milestones. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to the important factors discussed under the caption “Risk Factors” in our Quarterly Report on Form 10-Q for the quarter ended June 30, 2021 filed with the U.S. Securities and Exchange Commission (SEC) and our other filings with the SEC. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change.

Investor Contact:
Gitanjali Jain Ogawa
Solebury Trout
gogawa@soleburytrout.com  

Media Contact:
Julia Deutsch
Solebury Trout
jdeutsch@soleburytrout.com  

FAQ

What is ZN-c3 and its purpose in the clinical trial?

ZN-c3 is an oral WEE1 inhibitor being evaluated in a Phase 1/2 trial for its efficacy in combination with gemcitabine for patients with relapsed or refractory osteosarcoma.

When are the initial results from the ZN-c3 trial expected?

Initial results from the Phase 1/2 trial of ZN-c3 are expected in the second half of 2022.

What designations has Zentalis received for ZN-c3?

Zentalis has received orphan drug and rare pediatric disease designations from the FDA for ZN-c3.

What are the key endpoints for the ZN-c3 trial?

The primary endpoint for the ZN-c3 trial is event-free survival (EFS) at 18 weeks, with secondary endpoints including overall survival metrics.

What is the significance of the trial for ZNTL and its investors?

The trial's success could lead to important regulatory designations and market opportunities for ZNTL, impacting its stock performance positively.