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Research Field Cancer, Drug discovery

Heidelberg Heroes

The Medicine Maker recently explored two new projects in immune homeostasis and oral delivery of macromolecules launched by BioMed X – a German research institute with a very unique way of doing business and science (1).

For the sequel they sat down with the “Professor X” of Heidelberg, Christian Tidona, to discuss an oncology-focused collaboration with German pharma giant Merck KGaA (2).

When did BioMed X begin working with Merck?
 

Merck was our first partner at BioMed X – in fact, we’ve worked together since our launch in 2013. They have started nine different research groups with us, and, of the four that have been concluded, all were in the field of oncology.

Every BioMed X collaboration can be understood as a combination of incubation and outsourcing. Merck and others outsource early research problems to our institute in Heidelberg, and then we identify and incubate top research talent from universities around the world. From there, we run a “boot camp” and then select the best of the best to join the team and help solve the research problem. Big pharma companies cannot easily operate like this; we can because we work very close to academia.

Even the location of our institute reflects this. Heidelberg is a historic German town positioned on a beautiful riverside spot in the Neckar Valley, but it is also a famous university town, where around 160,000 inhabitants including 30,000 students and researchers in the life sciences live side-by-side. The German Cancer Research Center is here. The European Molecular Biology Laboratory is here. The Heidelberg University Hospital is here. And we are here!

Imagine throwing tennis balls at a man sitting on a four-legged chair. You win by knocking him off the chair, but how many tennis balls will you need? Too many. You need an alternative attack. What if you removed one of the chair legs? Now, your target is in trouble! Next, saw off a second leg. Checkmate!

How do the boot camps work?
 

We invite top research talents from different disciplines and different parts of the world to attend a five-day boot camp event. On the first day, we conduct an exercise called “My Life, My Work, My Passions.” Everybody presents in front of everyone else, and everybody takes notes. At the end of the day, we ask participants to rank each other with whom they would like to work together. We then feed those preferences into an algorithm, and it spits out an optimal composition of team members. 

On the next day, we disclose the team assignments, and everyone then stays in those groups for the rest of the boot camp. Then, the hard work begins – though the candidates tell us they enjoy it. 

At BioMed X, we don’t get by on hard work alone; diversity and cross-pollination are also key. The typical group leader in academia is surrounded by top people from their field of research, so the input and challenges they receive from their surroundings tend to be specific to their own topic. Our boot camps shake this up.

“Synthetic lethality and DNA repair” – what exactly is the focus of your latest partnership with Merck?
 

First of all, don’t be fooled by the rather complicated name – it’s actually not that complex; fundamentally, it’s about finding a way to making cancer cells much more sensitive to the most common first-line treatment options for cancer: radiation and chemotherapy.

A cancer cell is a cell that divides far more rapidly than most other cells in the body. If you hit it with radiation or chemotherapy, you introduce DNA damage. Since they divide less rapidly, normal cells have time to properly repair this damage and survive. Meanwhile, the rapidly dividing cancer cells suffer catastrophic events, and their genome simply disintegrates.

However, chemotherapy and radiation therapy are far from perfect. Most patients relapse because cancer cells have a wide array of DNA damage response tools at their disposal allowing them to become resistant to DNA damaging treatment. It is unfortunate that our opponent has such powers, but it’s also part of what motivates us. Our synthetic lethality project aims to identify new drug targets in DNA damage response pathways, which could decrease the probability of a relapse and increase the probability of curing the patient.

To understand the advantage of synthetic lethality, I’d like you to imagine throwing tennis balls at a man sitting on a four-legged chair. You win by knocking him off the chair, but how many tennis balls will you need? Too many. You need an alternative attack. What if you removed one of the chair legs? Now, your target is in trouble! Next, saw off a second leg. Checkmate!

Each leg of the chair represents a different DNA damage repair tool of a particular cancer cell, and the tennis balls represent radiation or chemotherapy. If we manage to switch off the DNA damage repair tools which are essential for the survival of a specific cancer cell using a new targeted therapy, the cancer cell will eventually die.

For this particular project, we must now deliver a starting point for Merck to embark on a fully-fledged drug discovery program. It’s true that we work closely with academia, but our goal is to bridge the gap to the pharma industry, so we ultimately want our research to result in a drug that will help patients.

What are your hopes for the future of your company?
 

As an entrepreneur, I have a long-term perspective. For BioMed X, there’s no exit story. I’m not going to sell it. I want to build something that will still exist in 100 years and create impact for the benefit of patients.

Grand visions aside, the next step is to test our model. We know it works in Heidelberg, but I want to see if it can scale to other locations and other technologies. To this end, we are launching our first proof-of-concept in Israel in a strategic partnership called AION Labs. At that site, following our model, we will jointly create 20 startups in the field of artificial intelligence for drug discovery and development over the next five years.

To start something like BioMed X, you need several ingredients coming together at the right time. In this case, the aligning star was brought to my attention by Dana Bar-On, head of academic relations at Israeli pharma company Teva – and a former BioMed X boot camp contestant; she called me about a tender being extended by the Israeli government. Specifically, they were inviting bids to build a local innovation ecosystem to attract the attention of global big pharma. We were joined by Pfizer, AstraZeneca, the German Merck, Amazon, and Israel Biotech Fund – and we won the tender. Now, we have the money and commitment to find out whether we can also build great startups, as well as outstanding research groups. And the great results of our first global call for application in Israel make us confident that we can!

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  1. A Stewart, “X2: Researchers United”, The Medicine Maker (2021). Available at: https://bit.ly/TMM-X2
  2. BioMed X, “Team SDR”, BioMed X (2022). Available at: https://bit.ly/bmx-sdr
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