Start-up for fundamentally new antibiotics

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The smartbax team of Robert Macsics, Stephan Sieber, Sylvia Varland and Eric Jus
The smartbax team of Robert Macsics, Stephan Sieber, Sylvia Varland and Eric Juskewitz is nominated at the Falling Walls Science Summit.
  • Smartbax nominated for Falling Walls Award

    It all started with basic research: During experiments in the laboratory, a team from the Technical University of Munich (TUM) discovered an active ingredient against multi-resistant bacteria that is fundamentally different from existing antibiotics. The researchers have since founded a start-up for the development of a novel drug. At the international Falling Walls meeting, the founders have been nominated for the ,,Science Breakthrough of the Year" in the Science Start-Up category.

    More and more bacteria are resistant to antibiotics. According to studies, hundreds of thousands of people die every year from infections with antibiotic-resistant pathogens. The hospital germ methicillin-resistant Staphylococcus aureus (MRSA) alone causes tens of thousands of deaths each year.

    A research team at TUM has discovered an active ingredient to which resistance of MRSA germs is extremely unlikely. While classic antibiotics attack either the cell wall or the metabolism of bacteria, we aim to permanently damage the protein transport and energy balance of the germs so that they no longer have the opportunity to multiply and develop resistance," explains Stephan Sieber, Professor of Organic Chemistry. Together with his former doctoral student Dr. Robert Macsics, he has founded a start-up to further develop the new active ingredient.

    Bacterial cell wall digests itself

    The foundation stone was laid in the TUM laboratories. "Initially, this was pure basic research," Sieber emphasizes. We tested hundreds of different active substances in cultures with Staphylococcus aureus and discovered a molecule that kills these bacteria very efficiently. With this molecule, we call it PK150, we then investigated the mode of action in the next step." The result: PK150’s mechanism of action is fundamentally different from that of conventional antibiotics. Instead of suppressing biochemical processes, PK150 stimulates the secretion of proteins in the cell wall. Important enzymes are expelled from the cell, and the wall begins to digest itself. At the same time, metabolism is blocked, the cell can no longer store energy and dies. Mutations with resistance to the active substance are extremely unlikely due to this dual mode of action.

    When it became clear that this molecule was a promising candidate for the development of a new antibiotic, we agreed that we wanted to further develop the active ingredient," recalls Sieber. "It is suitable for combating Staphylococcus aureus and other multidrug-resistant germs that have a Gram-positive, i.e. single-layer, cell wall." TUM first filed a patent application for the structure of the optimized molecule in 2017, while Sieber and Macsics went on an investor:in search. While the Corona pandemic was still underway, the two researchers won Boehringer Ingelheim Venture Fonds as an investor after a virtual pitch.

    Support in the TUM Venture Lab

    Shortly after, in 2021, they founded smartbax, one of the first startups to be accepted into the new TUM Venture Lab ChemSPACE. The TUM Venture Labs each specialize in one significant field of technology. They offer the founding teams specific technical infrastructure in this field, tailored training programs, expertise for the respective market and global networking with the industry. The opportunity to use the Venture Lab’s infrastructure and lab space helped us a lot in taking our first steps as an independent company," says Macsics, who became CEO of the startup after completing his doctorate. "Add to that the Venture Lab’s network, which continuously helps us build contacts."

    In the meantime, smartbax has three permanent employees, with Stephan Sieber acting as scientific advisor. In addition to further developing the active ingredient, the company is working on other strategies to eliminate resistant bacteria. In a few years, the first drug candidates should be ready for clinical trials.

    25 nominees from around the world

    The Falling Walls jury sees the team’s work as possibly one of the most important scientific breakthroughs of the year. To commemorate the anniversary of the fall of the Berlin Wall, the nonprofit Falling Walls Foundation always hosts the eponymous Science Summit in Berlin on November 9 to show a broad public the walls that science is breaking down. The event is considered one of the most important exchange formats between research and society as well as within science.

    Falling Walls selects the "Science Breakthrough of the Year" in five research fields and in the Science Start-Ups category. Smartbax is nominated along with 24 other start-ups from Europe, America, Asia and Australia.