Swiss biotech company Tolremo Therapeutics develops CBP/p300 bromodomain inhibitors to prevent non-hereditary cancers from developing drug resistance | Top 100 Swiss Innovators
Image source: Tolremo Therapeutics
The Swiss biotech company Tolremo Therapeutics (hereinafter referred to as Tolremo) was founded in 2017. The company is dedicated to the research and development of CBP/p300 bromodomain inhibitors. This inhibitor targets transcription cells, blocks the cancer drug resistance transcription pathway, and inhibits the development of drug resistance in non - hereditary cancers.
Tolremo is a spin - off company from the Swiss Federal Institute of Technology in Zurich, founded by Stefanie Flückiger - Mangual. Stefanie Flückiger - Mangual serves as the company's CEO and holds a Doctorate in Molecular and Translational Biomedicine from the Swiss Federal Institute of Technology in Zurich. She was previously a postdoctoral researcher at the same institute.
Image source: Tolremo Therapeutics
Tumors have a high incidence and mortality rate. Anti - tumor drugs are one of the main means of tumor treatment, but cancer drug resistance can seriously affect the efficacy of tumor treatment and often lead to tumor recurrence. Drug resistance is the tolerance of cancer cells to anti - tumor drugs. The main reasons for its development include gene mutations, changes in signaling pathways, and the influence of the tumor microenvironment. Although gene mutations can make cancer untreatable, non - genetic drug resistance can be reversed, for example, by targeting early transcriptional reprogramming to prevent the development of drug resistance.
Image source: Tolremo Therapeutics
Based on in - depth phenotypic research, Tolremo discovered a key mechanism governing the transcriptional resistance pathway and developed an oral small - molecule inhibitor of the CBP/p300 bromodomain. This inhibitor can be used as a monotherapy or in combination with targeted drugs for solid tumors and hematological malignancies to treat transcriptional non - oncogene addiction and significantly extend the duration of action of existing cancer therapies.
To prevent early cancer drug resistance, Tolremo screened small molecules that can down - regulate the non - hereditary cancer cell drug resistance phenotype and identified CBP/p300 as a novel drug resistance regulator. CBP and p300 are highly similar transcriptional co - activators involved in the regulation of gene expression. CBP/p300 is a clinically validated target for multiple myeloma. Previously, it was not known to be related to non - hereditary cancer drug resistance, but Tolremo's research found that CBP/p300 regulates a key transcriptional resistance pathway. Transcription refers to the process by which genetic information flows from DNA to RNA, and transcriptional reprogramming refers to the process by which cells reprogram their characteristics by changing the content and composition of intracellular transcripts in response to specific environmental stimuli to adapt to new physiological states or cope with external stress. Cancer cells use transcriptional reprogramming to evade targeted therapies. Transcriptional reprogramming driven by CBP/p300 enables cancer cells to activate bypass signaling, develop non - genetic resistance through bypassing the original signaling, epithelial - mesenchymal transition, stemness, and phenotypic plasticity, and achieve survival, proliferation, and spread.
Based on the above - mentioned unique target identification, Tolremo developed TT125 - 802. This is an orally available selective small - molecule inhibitor that targets the bromodomain of the transcriptional co - activator CBP/p300, preventing CBP/p300 from binding to histone - associated DNA, thereby blocking the upstream key mechanism of the early cancer transcriptional escape program, ensuring the efficacy of targeted therapies, and not interfering with pathways unrelated to cancer. Its pre - clinical potency, selectivity, and safety data indicate that this inhibitor has highly differentiated characteristics and can provide new clinical application opportunities for established targets and therapies.
Tolremo has demonstrated that TT125 - 802 can be used as a monotherapy or in combination with targeted drugs for solid tumors and hematological malignancies. When used in combination with targeted therapies such as KRAS, EGFR, and AR inhibitors, TT125 - 802 can provide more profound and long - lasting efficacy in pre - clinical models of non - small cell lung cancer, colorectal cancer, and prostate cancer. In November 2023, Tolremo announced the completion of its first - in - human clinical trial and the first patient dosing. In June 2025, Tolremo announced that TT125 - 802 is the first CBP/p300 inhibitor to show significant clinical activity in solid tumors, capable of achieving rapid, deep, and long - lasting efficacy in non - small cell lung cancer, colorectal cancer, and prostate cancer with KRAS - G12C and EGFR mutations, and demonstrating best - in - class safety without thrombocytopenia.
In September 2023, Tolremo completed a $39 million Series A financing round led by BioMedPartners, with participation from Pierre Fabre Invest, the second - largest private pharmaceutical group in France. The funds will be used to accelerate the clinical development of the core pipeline TT125 - 802. Next, Tolremo will continue to advance the clinical trials of TT125 - 802 to evaluate its efficacy in combination with targeted therapies for specific advanced tumors, including lung cancer with EGFR and KRAS mutations and multiple myeloma.
Tolremo Therapeutics is one of the companies on the "TOP100 Swiss Startups" list in 2024. The "TOP100 Swiss Startups" list brings together the best Swiss startups and growing technology innovation companies. It is the most internationally influential benchmark list in the Swiss technology innovation field. Since 2011, this list has selected 100 of the most innovative Swiss companies with the greatest market potential and 25 Swiss growing companies with the greatest unicorn potential across the country each year, covering fields such as life sciences, engineering machinery, robotics, information and communication, low - carbon technology, and food technology. The "TOP100 Swiss Startups" and related brand activities are iconic events in the Swiss innovation ecosystem, representing the highest level of Swiss innovation and the forefront of international investment and financing.
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