Experts: Stefanie Flückiger-Mangual (Tolremo)
Cancer cells are extraordinarily deceptive. They reprogram their inner workings, evade therapeutic intervention and even exploit tricks from embryonic development to outsmart the immune system. But Tolremo, a Swiss start-up, has discovered a groundbreaking active ingredient that disrupts these cellular deception tactics, offering renewed hope to cancer patients. Tolremo’s approach to developing new approaches is so innovative that it is surprising even seasoned researchers.
Tolremo
The immune system typically eliminates excessive cellular growth in the body with ruthless efficiency. But cancer cells play by entirely different rules. Despite facing hostile biological environments, they successfully deceive the immune system and reproduce without restraint. It is only in recent years that researchers have been able to shed light on cancer cells’ sophisticated survival strategies. They systematically reprogram signalling cascades that relay messages from cellular surface receptors to nuclear genetic material, thereby securing the essential nutrients and energy they need for their continued reproduction and survival.
When cancer medications attempt to block this reprogramming, tumour cells show astonishing adaptability, discovering alternative pathways to bypass detection by the immune system. Researchers have been astonished to observe how cancer cells activate other signalling cascades in such cases, including pathways that are normally only active during embryonic development. Consequently, around 40 per cent of cancer patients show no therapeutic response whatsoever, and even in initially successful treatments the cancer cells develop resistance to the drug within six to twelve months. The tumours reappear and resume their growth. This is why therapeutic strategies nowadays involve administering two drugs at the same time: one blocks the original signal transmission, while the other deactivates the alternative route.
Founded in 2017, Tolremo embarked on an ambitious quest through an extensive chemical library containing 16,000 distinct substances, seeking molecules capable of blocking cancer cells’ escape mechanisms. To do this, they used a patented screening technology incorporating tumour cells in test tubes, with the results interpreted using a simple binary system: the presence or absence of fluorescence. Cellular illumination following molecule introduction indicated successful blockage of escape cascade signalling. The absence of fluorescence meant the cancer cells’ survival pathways remained operational. TT125-802, the most promising discovery, was an optimised compound refined through a total of 802 iterative improvements. Understanding this compound’s precise operational mechanism required ingenious methodology. Researchers ultimately equipped TT125-802 with a kind of “molecular fishing rod”, introducing it into the cancer cell protein mixtures. This enabled them to isolate and definitively identify the target protein – the compound’s specific point of therapeutic attack.
This approach may sound deceptively straightforward, yet it is an exceptional innovation in cancer research, because most drug screenings typically start with the isolated target proteins whose activity requires blocking, followed by validation of the efficiency of protein-binding molecules in cancer cell testing. Stefanie Flückiger-Mangual, Tolremo’s co-founder and CEO, sums up this paradigm shift perfectly: “We essentially approached development of the active ingredient backwards – we were basically putting the cart before the horse.”
Two structurally almost identical proteins that are known to play a central role in the escape cascades, became caught on the molecular fishing rod. TT125-802 is highly specific and binds only to the activity centre of these two proteins, but not to similar structures in other proteins. Thanks to this specificity, fewer side effects are expected for patients, and the substance is promising for medical applications.
Tolremo focuses specifically on lung, prostate and colorectal cancers. During preclinical development, TT125-802 underwent rigorous testing on these cancers in both cellular models and mouse studies. The data demonstrated that combining TT125-802 with an established active agent results in superior, more durable tumour treatment outcomes compared to using the approved drug alone.
June 2025 marked a crucial milestone, when Tolremo published results from its ongoing first-phase clinical trial with cancer patients. Not only did the anticipated side effects fail to materialise, but treatment with TT125-802 slowed tumour progression or even induced tumour regression too. “Our concerns about giving patients false hope proved completely unfounded,” commented Stefanie Flückiger, a note of relief in her voice. TT125-802’s path forward seems to be clearly defined, and sale of the molecule to a large company for clinical approval is transitioning from an aspiration to an achievable reality.
This remarkable journey all began during Stefanie Flückiger’s doctoral thesis at ETH Zurich. Although she flourished in her research work, her visionary doctoral supervisor had to almost force her to make her own luck – or, more accurately, to found a company. After filing successful patent applications for the screening technology, he urged her to develop a business plan for potential investors over the course of a single weekend. No sooner said than done. Translating the innovative research concept and its further development into the plain language used in the business world required rapid adaptation. “I felt as if I was running down a mountain far too fast,” remarked Stefanie Flückiger, discussing that pivotal period in her life. Today, she is extremely grateful to her supervisor for his input. She is taking a big step closer to her ultimate goal: extending the lives of cancer patients. When it comes to inspiration, often all we need is a nudge in the right direction.
