Startup story #24 - MethylX

Most cancer therapies today fall short when it comes to tackling transcription factors (TFs), proteins traditionally considered “undruggable” that regulate gene expression and are involved in cancer development and growth. MethylX, a biotech spin-off originating from the USI-affiliated Institute for Research in Biomedicine (IRB) in Bellinzona, is developing a breakthrough antibody therapy that targets a methylated version of ERG (mERG), one of the key factors involved in prostate cancer. In this brief interview, Andrea Cavalli and Concetta Guerra share the story behind their project and mission to bring novel cancer treatments to life.

How did the story of MethylX begin?

It’s hard to pinpoint a single moment, MethylX has had several turning points along the way. It all started years ago with the discovery - made in collaboration with Carlo Catapano and Giuseppina Carbone from the IOR - that in prostate cancer certain transcription factors (TFs), proteins that regulate gene expression, undergo a specific chemical modification called methylation, which makes cancer cells more “aggressive”. This led to the development of a mini-antibody that selectively binds to the methylated form of a TF named ERG, effectively blocking its function. The most recent turning point came with the realisation that similar chemical modifications could occur in other cancers too: this insight to the development of a therapeutic platform that could be exploited to target a broader range of currently undruggable cancer drivers. Now we also have a complementary team to take the next steps. Andrea has a background in physics and mathematics, bringing in twenty years of experience in computational modelling and molecular simulation, while Concetta, trained in pharmaceutical biotechnology and cell biology, contributes to experimental research and translational applications.

What inspired you to turn your research into a startup project?

It wasn’t an immediate decision, rather something that developed gradually over time. As we continued working in the lab and began seeing strong, consistent results from our experiments, we started to realise the therapeutic potential of the discovery. The moment we understood that we were holding something that could have a real and tangible impact on the lives of cancer patients, it became clear that it was something worth taking beyond the lab.

How is your solution different from existing alternatives?

Transcription factors are a class of proteins that play a critical role in cancer progression but have long been considered “undruggable” due to their intracellular location and lack of well-defined binding pockets. Out of 2,000 known transcription factors, around 170 are linked to cancer, but only a few have ever been successfully targeted by existing therapies. What makes MethylX’s approach unique is the discovery of a cancer-specific chemical modification of the ERG transcription factor that occurs exclusively in tumour cells. Based on that, we designed a single domain antibody that selectively binds and blocks the modified version of ERG, leaving healthy cells unaffected. This opens the door to a completely new therapeutic space, leveraging a DNA-based delivery method that has already shown remarkable efficacy in laboratory studies.

What are the next milestones?

We’ve recently secured a grant from Innosuisse for an 18-month preclinical development phase in collaboration with IOR. During this time, we aim to finalize our IND-enabling package, to evaluate the safety and efficacy of our drug before it enters human clinical trials. Midway through, we plan to incorporate the company and refine our platform to start developing new therapies that target other cancer-related transcription factors, and eventually begin engaging with investors. The long-term goal is to create a robust pipeline of therapies, not just a single drug.

3 quick questions to wrap it up:

• How do you recharge your batteries? Running, studying and reading.
• Where do you see yourself in 10 years? Still pushing the project forward, transforming science into something that can truly impact patients’ lives.
• What’s the best piece of advice you’ve received so far? Surround yourself with people who bring skills and perspectives different from your own.