The startup develops investigational MDM2 inhibitors aimed at treating solid tumors and hematological malignancies. By targeting the MDM2 protein, the company provides a new therapeutic option that may enhance treatment outcomes for cancer patients.
Funding
Funding not disclosed
Founders
Product
Problem
In cancer cells, the tumor suppressor protein p53 is often rendered dysfunctional either through mutation or overexpression of its negative regulator, murine double minute 2 (MDM2), leading to unchecked cell proliferation. Existing cancer therapies may not effectively restore p53 function in these cases, limiting treatment options.
Solution
Kartos Therapeutics is developing navtemadlin (KRT-232), a potent and selective oral MDM2 inhibitor, as a therapeutic intervention for cancers with wild-type p53. Navtemadlin inhibits MDM2, thereby restoring p53 function, inducing cell-cycle arrest, and promoting apoptosis in cancer cells. Clinical studies have demonstrated that navtemadlin can induce cancer cell death by blocking DNA synthesis and increasing the expression of pro-apoptotic Bcl-2 family proteins. This approach offers a potential new treatment option for patients with selected solid tumors and hematological malignancies. Navtemadlin is being investigated both as a monotherapy and in combination with other anti-cancer agents.
Target Audience
The primary target audience includes patients with solid tumors and hematological malignancies, particularly those with myelofibrosis, acute myeloid leukemia, and Merkel cell carcinoma, whose tumors express wild-type p53.
Features
- Selective inhibition of the MDM2 protein
- Restoration of p53 function in cancer cells
- Induction of cell-cycle arrest and apoptosis
- Oral administration
- Demonstrated clinical activity in myelofibrosis, acute myeloid leukemia, and Merkel cell carcinoma
- Ongoing Phase 3 clinical trial (POIESIS) evaluating navtemadlin plus ruxolitinib in JAK inhibitor-naive myelofibrosis patients with suboptimal response to ruxolitinib
- Open-label Phase 1b/2 study assessing navtemadlin in combination with ruxolitinib in myelofibrosis patients with suboptimal response to ruxolitinib (NCT04485260)
- Phase 2 study assessing navtemadlin in Janus-associated kinase inhibitor treatment-naive myelofibrosis (NCT04878003)