Faeth Therapeutics has published promising preclinical data supporting its novel three-pronged approach to targeting cancer metabolism in endometrial and breast cancers. The findings, published in the British Journal of Cancer, demonstrate that simultaneous inhibition of multiple nodes in the PI3K/AKT/mTOR pathway, combined with dietary modification, can lead to significant tumor regression in preclinical models.
The company's PIKTOR strategy combines FTH-001 (serabelisib), a PI3Kα inhibitor, and FTH-003 (sapanisertib), an mTORC1/2 inhibitor, with an insulin-suppressing diet alongside paclitaxel chemotherapy. This approach targets the PI3K/AKT/mTOR pathway, which is crucial for metabolic signaling and highly mutated in hormone-sensitive cancers.
"Our latest preclinical findings underline the potential of our thesis, that combining targeted therapies with a precision diet can achieve superior outcomes in cancers where metabolism plays a crucial role," explained Dr. Oliver Maddocks, Chief Scientific Officer at Faeth Therapeutics and senior author of the study.
Addressing a Critical Pathway in Cancer
The PI3K/AKT/mTOR pathway is the most frequently mutated pathway in cancer and is essential for tumor metabolism. Endometrial cancer has the highest frequency of PI3K pathway mutations of any solid tumor, yet there are currently no approved therapies specifically addressing this vulnerability.
Previous attempts to inhibit this pathway using single-node inhibitors have resulted in modest efficacy and relatively high toxicity, particularly hyperglycemia. Faeth's multi-node inhibition approach aims to achieve a wider therapeutic window, potentially resulting in greater efficacy with fewer side effects.
Dr. Lewis Cantley, co-founder of Faeth Therapeutics, emphasized, "The integration of dietary interventions with targeted therapy is an essential advancement in cancer treatment, particularly for endometrial and breast cancers, which are linked to obesity and metabolic dysfunction. These results offer further compelling evidence that regulating insulin and metabolism enhances therapeutic efficacy."
Building on Clinical Promise
The preclinical findings build on encouraging early clinical data. In a Phase 1b study, the combination of serabelisib and sapanisertib with paclitaxel resulted in an 80% objective response rate in patients with endometrial cancer, with 11 months of progression-free survival.
In March 2025, Faeth launched a Phase 2 trial in collaboration with The GOG Foundation to evaluate this approach in patients with advanced or recurrent endometrial cancer. The study includes 40 patients and features a substudy that will specifically evaluate the impact of dietary modification on the therapeutic combination.
"This unique approach to target cancer metabolism has demonstrated impressive early results. We look forward to this trial to hopefully confirm these early findings and perhaps transform the way we treat patients with endometrial cancer," said Dr. David Starks, Principal Investigator and Associate Professor at Avera Cancer Institute and University of South Dakota Sanford School of Medicine.
Significant Unmet Need
Endometrial cancer is one of the leading causes of cancer death in women, with approximately 65,950 newly diagnosed cases in the United States in 2022. Despite currently available treatment options, nearly 12,550 endometrial cancer-related deaths were estimated in the U.S. that year.
Women with metastatic and recurrent endometrial cancer face particularly poor outcomes, with an estimated 5-year survival rate of just 20%. There is a high unmet need for effective treatments, especially for patients who have progressed after first-line carboplatin-based therapy.
Company Background and Platform
Faeth Therapeutics was founded in 2019 by oncology experts including Lew Cantley, Scott Lowe, Siddhartha Mukherjee, Greg Hannon, and Karen Vousden to focus on metabolism as an under-exploited pillar of cancer therapy.
The company leverages its AI-driven MetabOS™ discovery platform to identify metabolic targets and develop novel therapeutic approaches. Its lead program specifically addresses the PI3K/AKT/mTOR pathway, which is crucial for metabolic signaling and highly mutated in hormone-sensitive endometrial and breast cancers.
"Thanks to Faeth's ability to uncover novel metabolism-targeting strategies, we are positioned to leverage the PIKTOR approach for endometrial cancer and other solid tumors," said Anand Parikh, Chief Executive Officer of Faeth Therapeutics.
Looking Forward
Interim data from Faeth's Phase 2 clinical trial (NCT06463028) is anticipated by Q1 of next year, with complete results expected later in 2026. The company believes its multi-targeted approach has potential applications beyond endometrial cancer, particularly in other solid tumors where the PI3K/AKT/mTOR pathway plays a significant role in treatment resistance.
Dr. Brian Slomovitz, Director of Gynecologic Oncology at Mount Sinai Medical Center and Uterine Cancer Trial Lead for GOG Partners, noted, "Endometrial cancer is the leading cause of deaths among all gynecologic cancers. Finding better treatment options remains our highest priority. We are excited to partner with Faeth Therapeutics to further investigate this novel therapeutic approach."
