‘This reaction is so bloody obvious’

After completing his doctorate in Leiden, Marc Robillard had no clear career path in mind. Until he spotted an unusual vacancy in Nature: Philips Research was looking for a bio-inorganic chemist for a molecular medicine project. He had to Google that first, but it turned out to involve, among other things, drug targeting — the subject of his doctoral research.

Robillard was given the opportunity to set up a brand-new lab together with colleagues, including an animal facility and a cell culture, radiochemistry, and protein lab. In that buzzing R&D environment, ideas began to simmer. During a nap — ‘genuinely’ — Robillard suddenly hit upon a new idea, inspired by a paper by Carolyn Bertozzi that he had read during his doctorate. He envisioned a reaction mechanism that would make click chemistry applicable in living organisms for therapeutic purposes. ‘When I woke up I thought: this reaction is so bloody obvious. I immediately started writing a patent.’

‘On the Zuidas, we were laughed out of the room ten times in a row sometimes’

Toothbrushes

Philips was an innovative environment with considerable clout and budget, but ultimately the company decided to withdraw from its pharmaceutical division. Robillard was given a choice: continue working on coffee-extraction technology or contribute to a new generation of toothbrushes. But by then he had become so deeply intertwined with click chemistry that he decided to press on independently. ‘I was already married to the subject, really. When it ended at Philips, it became clear which path I had to take: starting my own company.’ No sooner said than done. At the end of 2011, Tagworks Pharmaceuticals was born.

Tagworks is developing a platform that combines click-to-release technology with, amongst other things, antibody-drug conjugates (ADCs). Not as a replacement, but as a complement to existing systems. Imagine a conventional ADC: an antibody that delivers a toxic payload to a tumour. Classical ADCs rely on binding to an internalising receptor for uptake by the cell, whereupon a protease releases the drug. An elegant system, but one with limitations. ‘Current ADCs work well, but only if the target receptor is taken up by the cell quickly enough. Many cancer types lack such a receptor.’ But that is not a problem, according to Robillard. ‘We make sure the drug is released ourselves.’

Tagworks designs ADCs in which the payload is chemically locked to the antibody via a bioorthogonal linker. Once the freely circulating molecules have cleared from the body, an external trigger is administered that, via the special click-to-release reaction with the linker, causes the drug to be released. ‘With this, we hope to treat tumour populations for which no ADCs currently exist.’

Clinical milestone

It sounds promising, but when Tagworks was founded, all of this was still a distant prospect. ‘When we left Philips, we had a click-to-release reaction in a test tube and a patent. We barely had any data. On the Zuidas, we were laughed out of the room ten times in a row sometimes. But you learn from every rejection.’ Right at the last moment, at the end of the first year, a major pharmaceutical partner expressed interest. ‘It wasn’t a mega-deal, but it kept us going for another year.’

‘We make sure the drug is released ourselves’

Then, at the start of 2025, the moment finally arrived: Tagworks’ ADC candidate TGW101 received approval from the American FDA to be tested in clinical phase 1. A crucial milestone: Tagworks is now permitted to treat humans with its technology for the first time. Over the coming year, around fifty patients will be recruited for the clinical study in the United States. Robillard had not initially expected that they would bring the technology to the clinical stage themselves. ‘The plan was to develop strong preclinical data, and then it might have been more efficient for a larger party to acquire the licences.’ However, the Tagworks technology involves two steps, which meant that more had to be demonstrated than with classical ADC technologies.

‘We weren’t following well-trodden paths. When it became clear that a preclinical deal wasn’t on the cards, we knew: we simply have to do it ourselves.’ Starting a company always carries risk. ‘We lived with uncertainty for a very long time, as a family too. You have to be able to cope with that,’ says Robillard. ‘We had a fine start with Philips. But ultimately it comes down to perseverance, making smart use of your resources, and working efficiently. And above all: talk to people — to investors, to pharma. Go to trade fairs. And write down every lesson you learn.’