Beyond the Oncogene: TOLREMO's New Weapon Against Drug-Resistant Cancer

BASEL, Switzerland – September 15, 2026 – In the relentless battle against cancer, drug resistance remains the final, formidable fortress. Tumors evolve, developing sophisticated workarounds to even the most advanced targeted therapies. Today, Swiss biotech firm TOLREMO therapeutics unveiled compelling data suggesting they may have found a key to unlock this fortress. At the 2026 World Conference on Lung Cancer (WCLC) in Seoul, the company presented final Phase I results for its drug, TT125-802, demonstrating a remarkable ability to shrink tumors in non-small cell lung cancer (NSCLC) patients for whom other treatments have failed.

The data provides the first strong clinical validation for a novel therapeutic strategy: targeting the cancer cell's addiction to its own survival machinery. By inhibiting a pair of proteins known as CBP/p300, TOLREMO aims to shut down the very transcriptional escape routes that cancer cells use to defy treatment, a move that could reposition the entire strategic chessboard of oncology.

A Clinical Breakthrough in Hard-to-Treat Cancers

The completed Phase I study of TT125-802 enrolled 45 patients with advanced solid tumors, including a cohort of 24 with NSCLC, a notoriously difficult cancer to treat once resistance emerges. The results were striking: 42% of these lung cancer patients (10 of 24) experienced tumor shrinkage from the monotherapy alone.

Crucially, these were not just any patients. The study included confirmed partial responses in three distinct and challenging resistance settings:

• Primary Resistance to EGFR Inhibition: A patient who failed to respond to the frontline standard-of-care, osimertinib.
• Acquired Resistance to KRAS G12C Inhibition: A patient whose tumor progressed after treatment with the targeted agent elironrasib.
• SOX2-amplified Squamous NSCLC: A patient with a difficult-to-treat subtype of lung cancer that had progressed after chemo-immunotherapy.

Showing single-agent activity in such diverse, heavily pre-treated populations is a significant achievement. It suggests that TT125-802 addresses a fundamental mechanism of resistance common across different genetic drivers. “This is precisely the kind of signal you hope for in an early-stage trial,” noted one oncologist not involved with the study. “It suggests the drug’s mechanism is hitting a core dependency, not just a niche pathway.”

Equally important for future development is the drug's safety profile. TOLREMO reported that 98% of treatment-related adverse events were mild and reversible, with the most common being taste disturbances and low-grade hyperglycemia. Critically, the study observed no thrombocytopenia (low platelet counts), a dose-limiting toxicity that has plagued other drugs in this class. This clean safety profile is a key strategic asset.

“The recommended dose of 60 mg once a day without food restriction delivers continuous target coverage and anti-tumor activity in drug-resistant NSCLC, while the favorable safety profile and absence of thrombocytopenia support the development of TT125-802 as a combination partner for targeted therapies,” said Alessandra Cesano, MD, Ph.D., Chief Medical Officer of TOLREMO.

The Science of Evasion: Shutting Down Cancer's Escape Plan

TOLREMO’s approach moves beyond attacking the primary genetic driver of a tumor—the oncogene—to focus on what it calls “non-oncogene addiction.” When a targeted therapy blocks an oncogene like EGFR or KRAS, cancer cells don't simply surrender. They activate parallel survival programs, a process known as transcriptional resistance. They effectively rewrite their own operating instructions to find a new way to grow.

This is where CBP/p300 come in. These two highly similar proteins act as epigenetic master regulators, helping to switch on clusters of genes that promote cell survival, proliferation, and drug resistance. By acetylating histones—the proteins around which DNA is wound—they open up the chromatin structure, making these pro-survival genes accessible for transcription. TT125-802 is a small molecule designed to inhibit the bromodomain of CBP/p300, effectively preventing them from docking at these critical genetic sites and initiating the resistance program.

The strategy is part of a broader, accelerating trend in oncology to target the epigenetic machinery that controls gene expression. While the concept has shown significant promise in hematological malignancies, its application in solid tumors has been more challenging. TOLREMO's data provides a powerful proof-of-concept that this approach is viable and potent in NSCLC.

A Strategic Validation with Broad Implications

The successful Phase I trial is more than a clinical milestone; it's a powerful validation of TOLREMO’s core scientific platform and business strategy. For a clinical-stage biotech, demonstrating clear monotherapy activity and a differentiated safety profile in a competitive field is a critical de-risking event that attracts investors and potential pharmaceutical partners.

“The completion of our Phase I marks an important milestone for TOLREMO and provides strong clinical evidence supporting our strategy of targeting non-oncogene addiction and transcriptional resistance mechanisms in cancer,” said Stefanie Flückiger-Mangual, Ph.D., CEO and Co-founder of TOLREMO. “The final data show durable monotherapy anti-tumor activity across biologically distinct forms of drug resistance in NSCLC. This validates our core scientific platform and positions TT125-802 as a foundational therapy.”

The field of CBP/p300 inhibition is gaining momentum, with companies like CellCentric and Pathos AI also advancing their own candidates. However, TOLREMO’s focus on diverse resistance settings in NSCLC and its favorable safety data carve out a strong competitive position. The absence of severe toxicities makes TT125-802 an ideal candidate for combination therapies, which is where its true value may lie.

The next logical step, as the company has indicated, is to move into combination studies. The ultimate goal is not just to treat resistance after it emerges, but to prevent it from ever taking hold. By simultaneously inhibiting the primary oncogenic driver with a targeted therapy and blocking the CBP/p300-dependent escape route with TT125-802, it may be possible to generate deeper, more durable responses. As CMO Alessandra Cesano noted, the company is now positioned to evaluate whether this dual-inhibition strategy can fundamentally change patient outcomes. The results from WCLC suggest they are well on their way to finding out.