20 January 2023 - - US-based Cyteir Therapeutics, Inc (NASDAQ: CYT) has announced the strategic prioritization of clinical development of CYT-0851, an investigational monocarboxylate transporter inhibitor, as a potential combination therapy for the treatment of ovarian cancer, the company said.

The prioritization follows encouraging preliminary clinical activity in a small number of patients observed in the Phase 1 dose escalation cohort with CYT-0851 in combination with capecitabine in advanced ovarian cancer.

Cyteir plans to expand its evaluation of CYT-0851 in combination with capecitabine to treat advanced ovarian cancer and enroll additional patients in the first half of 2023 to further support these early signals.

If successful, the combination of CYT-0851 with capecitabine has the potential to be an all-oral treatment for ovarian cancer.

In conjunction with focusing clinical activities on ovarian cancer, Cyteir is reducing headcount by approximately 70% and deferring research and development in other areas, which is expected to extend Cyteir's cash runway into 2026.

CYT-0851 Development to Prioritize Combination Therapy

Phase 1 dose escalation cohorts with CYT-0851 in combination with capecitabine for the treatment of advanced ovarian cancer have shown encouraging preliminary clinical activity.

To date, thirteen patients have been treated with CYT-0851 (from 100-400mg daily) and capecitabine, including five patients with advanced ovarian cancer.

Responses and disease stabilization observed in these ovarian cancer patients in the 300mg and 400mg CYT-0851 dose levels are encouraging, and have led to Cyteir's decision to focus on further development of this capecitabine combination in advanced ovarian cancer.

Overall, CYT-0851 continues to be generally well tolerated with no new safety concerns.

In the first quarter of 2023, Cyteir expects to determine a maximum tolerated dose for CYT-0851 in combination with capecitabine and focus its efforts on enrolling and treating additional patients with advanced ovarian cancer at the MTD.

If the data from these additional patients further support Cyteir's focus on ovarian cancer, Cyteir intends to pursue development and potential registration of CYT-0851 in combination with capecitabine as an all-oral treatment for platinum resistant ovarian cancer.

In addition, Cyteir is evaluating CYT-0851 in Phase 1 dose escalation cohorts in combination with gemcitabine. To date, ten patients have been treated with CYT-0851 (from 100-200mg daily) and gemcitabine.

Cyteir will continue the ongoing dose escalation cohorts with CYT-0851 and gemcitabine in solid tumor patients to identify an MTD, which could provide an additional opportunity to develop CYT-0851 as a combination therapy to treat patients with platinum resistant ovarian cancer.

Enrollment in the Phase 2 monotherapy cohorts with CYT-0851 will be suspended due to insufficient monotherapy activity observed to date. Cyteir plans to disclose the Phase 1 combination data for CYT-0851 in mid-2023.

In the United States, it is estimated that a total of approximately 13,000 patients are available for drug treatment per year who are platinum resistant and have progressed after two lines of prior therapy, or have progressed after at least three prior lines of therapy.

Cyteir is a clinical-stage oncology company that is focused on the development of CYT-0851, an oral investigational drug that inhibits monocarboxylate transporters.

Cyteir's current priority in CYT-0851 development is in combination with capecitabine and gemcitabine in a Phase 1/2 clinical study, including patients with advanced ovarian cancer.

Capecitabine is a nucleoside metabolic inhibitor that is approved in the US for the treatment of patients with adjuvant colon cancer, metastatic colorectal cancer, and metastatic breast cancer.

It is an orally administered systemic prodrug of 5'-deoxy-5-fluorouridine (5'-DFUR) which is converted to 5-fluorouracil.

Gemcitabine is approved in the US in combination with carboplatin for the treatment of ovarian cancer, in combination with paclitaxel for the treatment of breast cancer, in combination with cisplatin for treatment of non-small cell lunch cancer, and as a single agent for the treatment of pancreatic cancer.

Gemcitabine kills cells undergoing DNA synthesis and blocks the progression of cells through the G1/S-phase boundary.