New $25 million raise advances multi-node PI3K program; randomized phase 2 trial with Gynecologic Oncology Group Foundation now enrolling

Faeth Therapeutics, a clinical-stage biotechnology company advancing therapies that systematically target tumor metabolism, today announced the advancement of its lead PIKTOR regimen in endometrial cancer and a $25 million strategic raise, bringing total capital raised to $92 million. The financing was led by S2G Investments with participation from existing investors Khosla Ventures, Future Ventures, Digitalis Ventures, KdT Ventures and Cantos, plus new investors B Capital Group, Avicella and THO Seed Fund. Clinical data from sapanisertib in combination with paclitaxel, one component of the PIKTOR regimen, have been selected for a late-breaking oral presentation at the ESMO 2025 Congress.

Faeth's phase 1b study of serabelisib + sapanisertib ("PIKTOR") with paclitaxel demonstrated an 80% overall response rate in endometrial cancer patients, with a median progression-free survival of 11 months versus historical 3-4 months with chemotherapy alone. The strength of these results led the Gynecologic Oncology Group (GOG) Foundation, one of the premier U.S. clinical trial networks, to initiate a phase 2 trial (GOG-3111; NCT06463028), now enrolling patients. The study also includes a predefined substudy testing whether protocolized insulin control under trial conditions through precision nutrition enhances clinical outcomes.

Endometrial cancer is one of the highest-need solid tumors and illustrates how Faeth’s approach can change outcomes in diseases where PI3K/AKT/mTOR are implicated. This signaling axis is among the most frequently altered across solid tumors, including endometrial, breast, lung, and ovarian. Current single-node inhibitors often fail due to feedback reactivation and mutations elsewhere in the pathway that limit durability. These inhibitors can only target a small fraction of patients with pathway mutations.

Faeth's approach is different: it delivers selective multi-node inhibition at PI3Kα, mTORC1, and mTORC2 while controlling the nutrient supply tumors depend on. Multi-node inhibition of the PI3K/AKT/mTOR pathway has already shown clinical benefit in phase 3 studies, confirming the value of pathway-level control in both mutant and wild-type tumors. Faeth’s selective approach builds on this validation while targeting specific nodes to improve the therapeutic window compared to pan-pathway inhibitors, offering less toxic, more convenient treatment options. In preclinical models, this multi-node approach achieved more complete pathway shutdown than single-agent inhibition.

"We've achieved the optimal balance in PI3K pathway inhibition, comprehensive enough to prevent resistance, selective enough to avoid immunosuppression," said Anand Parikh, CEO of Faeth Therapeutics. "The 80% response rate, 11-month progression-free survival, initiation of a trial by the GOG Foundation, and recognition as a late-breaking oral presentation at ESMO show that Faeth is executing as a clinical-stage company positioned to expand across the solid tumors where PI3K alterations drive disease."

“I believe recent phase 3 studies are showing validation of multi-node targeting,” said S2G Managing Partner Sanjeev Krishnan. “In my view, insider participation in this financing reflects conviction in Faeth’s progress, while new investors recognize metabolism as a category entering the clinic. Based on emerging evidence, Faeth’s selective multi-node approach appears well suited to capture value as metabolism gains recognition as a potential new pillar of cancer treatment."

The $25 million will advance the phase 2 endometrial cancer program through a full data readout in Q3 2026 and expand throughput for the company's MetabOS™ platform. The financing also supports a phase 1 study in locally advanced rectal cancer for Faeth’s non-essential amino acid restricted program and initiation of Faeth's first non-oncology program in Hereditary Tyrosinemia Type 1 (HT1), a rare pediatric metabolic disorder, with IND-enabling studies targeting Q4 2026 clinical entry.

Beyond blocking growth signals, Faeth's approach recognizes that tumors have significantly elevated metabolic demands and require specific nutrients to survive. The MetabOS platform integrates genomic, gene expression, and tumor microenvironment data to identify metabolic dependencies and exploit them clinically. Funding will expand MetabOS throughput, enabling Faeth to simulate and validate more regimens designed to address metabolic escape.

"If the cell is the unit of life, then metabolism is the first verb in its sentence," said Siddhartha Mukherjee, co-founder of Faeth Therapeutics. "Faeth is intervening where cellular decisions are made fastest: at the metabolic switches tumors rely on to adapt, long before mutations accumulate. That is why metabolism is emerging alongside the genome and immunogenicity as a therapeutic discipline."

In addition to its oncology programs, Faeth has initiated translational work to treat HT1, an ultra-rare disorder affecting 1 in 100,000 births, where toxic metabolites accumulate due to an enzyme deficiency. While current treatment prevents liver failure, patients still face unmet medical needs. The company is applying MetabOS to develop metabolic therapeutic approaches for this condition. This program is the first demonstration of MetabOS applied outside of oncology and establishes the platform’s ability to identify and address metabolic dependencies across diseases.

About Faeth Therapeutics

Faeth Therapeutics is a clinical-stage biotechnology company developing multi-node therapies that block cancer growth signals while controlling tumor fuel supply, leveraging its AI-driven MetabOS™ platform to identify and exploit metabolic dependencies. In addition to advancing multiple solid-tumor studies, Faeth is advancing a translational program in Hereditary Tyrosinemia Type 1 (HT1), the first example of how its approach can extend beyond oncology into rare diseases. Founded in 2019 by leading researchers including Lewis Cantley, PhD, Siddhartha Mukherjee, MD, DPhil, Karen Vousden, PhD, Scott Lowe, PhD, and Greg Hannon, PhD, the company has raised $92 million from S2G Investments, Khosla Ventures, Future Ventures, Digitalis Ventures, KdT Ventures, Cantos, Avicella, THO Seed Fund, and B Capital Group. For more information, visit faeththerapeutics.com.

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