Our Pipeline

Zentalis develops small molecule therapeutics with differentiated product profiles for a broad range of cancers.

Zentalis Pharmaceuticals is conducting clinical studies evaluating its small molecule therapeutics.
Clinical Trials
Compound
Indication
Trial Name + Development Approach
Phase 1
Phase 2
Phase 3

Azenosertib Being Studied As Monotherapy And Combination In Multiple Tumors

Studies for Lead Indication
Other Studies Ongoing
PROC
Monotherapy
DENALI Part 1b
Phase 2
PROC
Monotherapy
DENALI Part 2
Registration-intent
Cyclin E1+
FDA Fast Track Designation
Phase 2
PROC
Monotherapy
Randomized Confirmatory Study
Azenosertib vs. SOC chemo
Cyclin E1+
Phase 3
Uterine Serous Carcinoma
Monotherapy
TETON (ZN-c3-004)
FDA Fast Track Designation
Phase 2
Ovarian Cancer
Combination
ZN-c3-002
Azenosertib + multiple chemo backbones and bevacizumab
Phase 1
BRAF Mutant Colorectal cancer
Combination
ZN-c3-016
Azenosertib + encorafenib and cetuximab
Phase 1

Ongoing Study

Planned Study

Product Candidates

Azenosertib WEE1 Inhibitor

Azenosertib is a potentially first-in-class and best-in-class small molecule Wee1 inhibitor in development for the treatment of cancer. Inhibition of WEE1, a DNA damage response kinase, drives cancer cells into mitosis without being able to repair damaged DNA, resulting in cell death. Currently, there are no FDA-approved WEE1 inhibitors, and we have designed Azenosertib to have advantages over other investigational therapies, including superior selectivity and pharmacokinetic properties.

Azenosertib is being developed in three therapeutic settings of high unmet need:
As a monotherapy
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In combination with traditional chemotherapy and DNA damaging agents
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In combination with molecularly targeted agents
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  • WEE1 is a protein kinase that inhibits the activity of both CDK1 and CDK2 kinases and is involved in the regulation of G1/S, G2/M, and M phase cell cycle checkpoints
  • WEE1 plays an important role during normal cell cycle progression but also in response to DNA damage and interacts with DNA damage response (DDR) pathways
  • WEE1 inhibition causes cancer cells to proceed into mitosis without being able to repair damaged DNA, resulting in prematuremitotic entry andapoptosis
  • WEE1 inhibition also increases replication stress by inducing aberrant firing of replication origins and depletion of nucleotide pools

Azenosertib mechanism of Action

  • WEE1 plays a crucial role in cell cycle regulation and DNA damage response (DDR) in both non-malignant and cancer cells​
  • WEE1 phosphorylates CDK1 and CDK2 and negatively regulates CDK/ Cyclin complexes to inactivate them​
  • Inactive Cyclin/CDK complexes permit cell cycle arrest at checkpoints, allowing cells to repair DNA damage before mitosis​
  • Cells with functioning WEE1 can repair their DNA adequately and effectively proliferate
  • When WEE1 is inhibited by azenosertib in cancer cells, Cyclin/CDK complexes remain unphosphorylated and activated
  • Active Cyclin/CDK complexes allow the cell cycle to progress without repairing DNA damage
  • Azenosertib causes cancer cells to accumulate DNA damage, resulting in replication stress, mitotic catastrophe and apoptosis
  • CCNE1 gene amplification is a common oncogenic driver in many solid tumors, including high grade serous ovarian carcinomas
  • Both CCNE1 gene amplification and high Cyclin E1 protein expression have been associated with chemotherapy resistance and poor patient outcomes1
  • Cyclin E1 overexpression, which can also occur in the absence of CCNE1 gene amplification, increases CDK2 activity and accelerates G1/S transition2
  • Cyclin E1 overexpression results in replication stress and renders cells more dependent on the WEE1 G2/M cell cycle checkpoint 2