Oncternal Therapeutics is a clinical-stage oncology company focused on developing innovative therapies for hematological malignancies and prostate cancer. One of their key candidates, ONCT-534, is a Dual-Action Androgen Receptor Inhibitor (DAARI) designed to target metastatic castration-resistant prostate cancer (mCRPC) and other diseases driven by androgen receptors. This investigational drug is unique in its mechanism of action, as it binds to both the N-terminal domain and the ligand-binding domain of the androgen receptor, leading to the degradation of the receptor and inhibition of its function. This approach aims to address the significant clinical need for effective treatments in patients who have developed resistance to existing androgen receptor inhibitors, which often occurs due to mutations or splice variants of the receptor.

In addition to ONCT-534, Oncternal is also developing ONCT-808, a CAR T-cell therapy targeting the ROR1 protein, which is expressed in various human cancers. This therapy aims to harness the body’s immune system to attack cancer cells more effectively. The company’s research emphasizes the importance of targeting novel biological pathways that are often overlooked in traditional cancer therapies, thereby providing new avenues for treatment in cancers with critical unmet needs. Through these innovative approaches, Oncternal Therapeutics is committed to advancing the field of oncology and improving outcomes for patients facing challenging cancer diagnoses.

United States

Oncternal Therapeutics is a clinical-stage oncology company developing first-in-class, novel therapies that target a broad spectrum of cancers with large unmet medical need. By leveraging pathways absent or minimally expressed in normal cells or tissue, we aim to inhibit cancer cell growth while reducing potential harm to healthy cells. We are pursuing trials in chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), breast cancer, and Ewing sarcoma. Looking forward, we intend to rapidly broaden our pipeline and invest in the development of our innovative therapies across multiple cancers.

Cancer

Hematologic Diseases

Urogenital Diseases

Oncternal Therapeutics

B-cell lymphoma

Hematologic malignancies

Chimeric antigen receptor T-cell (CAR-T) therapies are T cells that &nbsp;have been engineered to target and engage a specific marker on cancer &nbsp;cells in an effort to direct an immune response against those cancer cells. CAR-T therapies have shown dramatic effects as treatments &nbsp;of CD19-expressing leukemias and lymphomas and BCMA-expressing myeloma. ROR1 is highly expressed on many solid and hematologic cancers but not often expressed on healthy tissue.
CAR T

ONCT-808 (CAR-T)

Relapsed/refractory Ewing sarcoma

TK216 is a first-in-class small molecule inhibiting the biological &nbsp;activity of ETS-family (E26 Transformation - Specific) transcription &nbsp;factor oncoproteins in a variety of tumor types. It is currently &nbsp;being evaluated alone and in combination with vincristine in a Phase 1 &nbsp;study in patients with relapsed or refractory Ewing sarcoma, a pediatric bone &nbsp;cancer.

ONCT-216 (TK216) (EWS-FLI1 inhibitor)

Metastatic breast cancer

Cirmtuzumab is a first-in-class humanized monoclonal antibody that binds &nbsp;with high affinity to a biologically important epitope on ROR1 &nbsp;(Receptor-tyrosine kinase-like Orphan Receptor 1). ROR1 is a type 1 &nbsp;transmembrane protein, essential for fetal development, that is &nbsp;expressed on the plasma membrane with an extracellular domain that is essential for ligand &nbsp;binding and signal transduction. Cirmtuzumab binds to many different &nbsp;types of cancer cells, but does not recognize most normal adult tissues.

Zilovertamab (Cirmtuzumab) (ROR1) + Paclitaxel

Blood cancer

Chronic lymphocytic leukemia

Mantle cell lymphoma

Zilovertamab (Cirmtuzumab) (ROR1) + Ibrutinib 

Castration-resistant prostate cancer

ONCT-534, our Dual-Action Androgen Receptor Inhibitor (DAARI) candidate, is a novel investigational, potentially first-in-class, orally bioavailable, dual-action androgen receptor (AR) inhibitor, designed to treat patients with metastatic castration-resistant prostate cancer and other androgen receptor-driven diseases. Based on preclinical studies, we believe ONCT-534 has the potential to be a novel treatment option for patients with advanced resistant prostate cancer. We licensed ONCT-534 and certain other DAARI program rights from the University of Tennessee Research Foundation, or UTRF, under an exclusive, worldwide license agreement.
 
As a Dual-Action Androgen Receptor Inhibitor or DAARI, ONCT-534 has a potentially novel and unique mechanism of action: it interacts with both ends of the AR, the N terminal domain (NTD) and the LBD, inhibiting AR function and leading to AR protein degradation. We believe that this NTD binding is relevant to the activity of ONCT-534 against tumors expressing AR splice-variants by preventing AR activation. In this respect, ONCT-534 is designed to mechanistically differ from classical non-steroid antiandrogens that interfere with androgen synthesis, such as abiraterone, and to differ from current standard of care treatment options, such as enzalutamide, darolutamide, &nbsp;or apalutamide, that bind only to the LBD of the AR, which may explain their reduced efficacy in patients with AR-SV-expressing tumors, as these AR variants lack most or all of the LBD. We believe that the differentiated dual-action pharmacology of ONCT-534 has the potential to help men with prostate cancer that is resistant to current standard of care treatments by virtue of amplified AR, LBD mutations, or AR splice variants with loss of LBD. &nbsp; Importantly, ONCT-534 is also active in preclinical models of prostate cancer with a normal, unmutated AR.
CAR T

Oncternal Therapeutics

Company Details