Our Pipeline

Our Pipeline

CompoundComp
IndicationInd
Development ApproachDev
PreclinicalPre
Early Clinical DevelopmentEarly
Late Clinical DevelopmentLate
ZN-c3
Wee1 Inhibitor
Uterine Serous Carcinoma
Monotherapy

ZN-c3
Wee1 Inhibitor

Uterine Serous Carcinoma
Solid Tumors
Monotherapy
Solid Tumors
Cyclin E Driven High Grade Serous Ovarian
Monotherapy
Cyclin E Driven High Grade Serous Ovarian
PARP Resistant Ovarian Cancer
Monotherapy alternating with niraparib or concurrent with niraparib
PARP Resistant Ovarian Cancer
Ovarian Cancer
+ Multiple Chemotherapy Backbones
Ovarian Cancer
Osteosarcoma
+ gemcitabine
Osteosarcoma
BRAF Mutant mCRC
+ encorafenib and cetuximab
BRAF Mutant mCRC
Pancreatic Cancer
+ gemcitabine
Pancreatic Cancer
ZN-d5
BCL-2 Inhibitor
AL Amyloidosis
Monotherapy

ZN-d5
BCL-2 Inhibitor

AL Amyloidosis
NHL
Monotherapy
NHL
AML
+ ZN-c3
AML
BCL-xL
Degrader
Solid Tumors and Heme Malignancies

BCL-xL
Degrader

Solid Tumors and Heme Malignancies

Product Candidates

ZN-c3 is a potentially first-in-class and best-in-class small molecule Wee1 inhibitor in development for the treatment of cancer. The inhibition of Wee1, a DNA damage response kinase, drives the accumulation of DNA damage in cancer cells, causing cell death, preventing tumor growth and potentially causing tumor regression. Currently, there are no FDA-approved Wee1 inhibitors, and we have designed ZN-c3 to have advantages over other investigational therapies with superior solubility, selectivity, and PK properties.

We have established a three-pronged development plan for ZN-c3 – investigation as a monotherapy, in combination with chemotherapy, and in combination with targeted therapies – and we are currently evaluating this candidate in several ongoing and planned studies. As a monotherapy, we are investigating ZN-c3’s potential in uterine serous carcinoma (USC), in solid tumors, and in Cyclin E protein overexpression and gene amplification in high-grade serous ovarian cancer, our biomarker strategy. In addition, there is strong data demonstrating Wee1 inhibition’s synergy with DNA-damaging therapies, such as PARP inhibitors, and with targeted agents in mutationally driven cancers. There is significant interest in these approaches, and we currently have collaborations with Pfizer, GSK and the Dana-Farber Cancer Institute to explore these combinations in the clinic.

ZN-d5 is a small molecule selective inhibitor of B-cell lymphoma 2 (BCL-2), in development initially for the treatment of hematologic malignancies and related disorders. BCL-2 and BCL-xL are proteins that play a critical role in the regulation of cell death. The overexpression of BCL-2 and/or BCL-xL are frequently detected in numerous cancer types, which prevent apoptosis of cancer cells. We believe a BCL-2 inhibitor may restore the normal apoptosis process, making it an important target for cancer treatments. Utilizing our medicinal chemistry expertise, we have designed ZN-d5 to have optimized potency, selectivity and PK.

We believe ZN-d5 is an attractive candidate and is being evaluated as a monotherapy and in combination with other therapies. We are currently conducting a Phase 1 trial of ZN-d5 in patients with Non-Hodgkin’s lymphoma (NHL), a Phase 1/2 trial in patients with relapsed or refractory Light Chain (AL) amyloidosis, and our planned Phase 1/2 combination trial with ZN-c3 in acute myeloid leukemia (AML).

BCL-xL is a member of the anti-apoptotic BCL-2 proteins. Its overexpression in tumor cells contributes to tumor survival and therapeutic resistance mechanisms. While a promising, clinically validated target, BCL-xL inhibition has failed in the clinic due to dose limiting on-target thrombocytopenia. Since the degradation machinery in platelets is impaired, a degradation approach for BCL-xL has been proposed to reduce the risk of  thrombocytopenia. Therefore, we believe a BCL-xL degrader may enable clinical efficacy to be achieved at lower doses and frequencies, further reducing the chance of thrombocytopenia and increasing therapeutic index. We recently initiated IND-enabling activities on our BCL-xL degrader development candidate. Our molecule is designed to have platelet sparing benefits over clinical-stage BCL-xL targeted inhibitors and has demonstrated potent anti-cancer activity in several preclinical models