Faeth Therapeutics Shows Preclinical Proof-of-Concept for Drug-Diet Combination to Treat Cancer, in Peer-Reviewed Publication

• Findings published in the peer-reviewed British Journal of Cancer highlight novel, three-pronged approach for metabolism-driven endometrial and breast cancers
• Combination, now in Phase 2, builds on earlier clinical efficacy signals for serabelisib-sapanisertib combination, adding an insulin-suppressing diet
• Preclinical findings confirm potential of Faeth’s rationale for multi-node PIKTOR inhibition to overcome common treatment resistance mechanisms

AUSTIN, Texas–(BUSINESS WIRE)–Faeth Therapeutics, a clinical-stage biotechnology company integrating precision nutrition with combination therapies to address cancer metabolism, today announced publication of a preclinical proof-of-concept study supporting its rationale for targeting cancer metabolism through multi-node inhibition, including both therapeutics and an insulin-suppressing diet. The findings, published today in the peer-reviewed British Journal of Cancer, show that the three-pronged PIKTOR approach – using Faeth’s dual PI3K/AKT/mTOR pathway inhibitors FTH-001 (serabelisib) and FTH-003 (sapanisertib) along with dietary modification, added to paclitaxel – demonstrated tumor regression in endometrial and breast cancer models. In March, Faeth launched a Phase 2 trial with The GOG Foundation using this PIKTOR strategy in patients with endometrial cancer, the cancer most strongly linked to obesity and metabolic syndrome.

Faeth was founded in 2019 by oncology luminaries, including Lew Cantley, Scott Lowe, Siddhartha Mukherjee, Greg Hannon, and Karen Vousden to focus on metabolism as an under-exploited pillar of cancer therapy. Its lead program addresses the PI3K/AKT/mTOR pathway, which is crucial for metabolic signalling and highly mutated in hormone-sensitive endometrial and breast cancers. Previous biopharma efforts targeting the pathway produced modest therapeutic results, typically due to resistance mechanisms or safety concerns.

However, Faeth has in-licensed FTH-001 and FTH-003 based on their potential to optimally target key nodes of the PI3K pathway in combination: in a Phase 1b study, adding the combination to paclitaxel resulted in an 80% ORR in for patients with endometrial cancer¹. Its recently launched Phase 2 trial, including 40 patients with advanced or recurrent endometrial cancer, includes a substudy that will evaluate the impact of dietary modification on this therapeutic combination. Today’s new publication spells out, for the first time, Faeth’s therapeutic rationale and presents in vivo evidence of efficacy to support the incorporation of an insulin-suppressing diet.

“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. “This multi-targeted approach substantially inhibited tumor growth in preclinical models, providing strong justification for its ongoing clinical investigation. Given the role of PI3K/AKT/mTOR signalling in cancer resistance to paclitaxel and other common therapeutics approaches, we see potential for multi-node inhibition strategies in other solid cancers as well.”

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.”

Previous attempts at inhibition of the PI3K/AKT/mTOR signaling pathway using single-node inhibitors have resulted in modest efficacy and relatively high toxicity, particularly hyperglycaemia. However, Faeth’s approach to simultaneously target multiple specific mechanisms via diet and therapeutics aims to achieve a wider therapeutic window, resulting in greater efficacy with lower toxicities like hyperglycemia. The new paper details the results of combining the mTORC1/mTORC2 inhibitor FTH-003, the PI3Kα inhibitor FTH-001 and an insulin-suppressing diet, on top of chemotherapy. 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 new publication, “Multi-node inhibition targeting mTORC1, mTORC2 and PI3Kα potently inhibits the PI3K/AKT/mTOR pathway in endometrial and breast cancer models,” published online today in British Journal of Cancer.

About Faeth Therapeutics

Faeth Therapeutics is a clinical-stage biotechnology company integrating targeted therapies with precision nutrition interventions to exploit metabolic vulnerabilities in cancer. Founded by renowned researchers from Cornell, Columbia, Cambridge, Memorial Sloan Kettering, and the Crick Institute—including Drs. Lewis Cantley, Siddhartha Mukherjee, Karen Vousden, Greg Hannon, and Scott Lowe—Faeth leverages its AI-driven MetabOS™ discovery platform to identify metabolic targets. Its lead clinical program, combining serabelisib, sapanisertib, and dietary intervention, aims to disrupt the PI3K/AKT/mTOR pathway, demonstrating promising outcomes in cancers strongly associated with obesity and metabolic disorders. For more information, visit www.faeththerapeutics.com.

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