Reaching new antibody heights

Antibodies are biological products increasingly used to develop treatment optionsfor a range of indications, from cancer to infectious diseases.  The courage and passion of Roche Pharmaceutical Research and Early Development (pRED) scientists to follow the science behind antibodies has taken them on many different journeys, with highs and lows along the way. We take a look at the last decade of Roche’s breakthrough science and how it has delivered new directions for antibody therapeutics in the fight against debilitating diseases for patients around the world.

For Roche pRED scientists like Christoph Ullmer, Senior Principal Scientist, the peaks and valleys of early pharmaceutical research are familiar grounds. They reflect on more than a decade of blazing trails in bringing antibody therapeutics to new disease areas, and how the Roche pRED team was uniquely equipped to see the paths forward where no one else had. 

“I am a strong believer in technology-driven innovation,” Christoph Ullmer explains. pRED’s advancements in bringing antibody technologies to new areas of need have been made not just by leveraging their understanding of a disease’s biology, but have also been founded on developments in the antibody engineering technologies required to make an investigational molecule in the first place. 

What really enables the Roche pRED scientists to break new ground is their collective ability to think outside the box with their new technological tools. Roche allows employees the freedom to pursue unconventional ideas. The team was able to identify that the mode of action of a cancer drug candidate might allow it to have a therapeutic effect in a completely different indication. The scientists had a moment of inspiration when they saw a mechanistic overlap between two different pathologies, which opened a new way forward. The collaborative nature of the wider team allowed those first inklings of an idea to flourish into a shared goal. The team was able to launch a project for a disease area that, at the time, was not being investigated by pRED, but evaluated and championed an idea to show its potential.

Bringing a drug from the benchtop to the bedside is not a clear and easy path, and there are many that fail along the way. After developing and screening for an initial drug candidate, optimising that molecule for a given disease area will have its own suite of scientific challenges. Scientists must ensure the stability and bioavailability of any new drug candidate in whichever part of the body it is administered to. Sensitive and highly vascular regions in the body may need new drug options to be designed to reduce the risk of unwanted effects. 

Roche has a long heritage in antibody engineering, having been one of the first companies to break into the space in the 1970s and being a pioneer in adopting bispecific antibodies. The specificity and power the scientists can exercise when designing new antibodies have come a long way since then. The innovation of Roche’s CrossMAb technology in 2011 allowed scientists to imagine new modes of action for bispecific antibodies, given the potential of binding to more than one molecular target with a single antibody, and the ability to reliably produce such complex antibody therapeutics. 

Christoph comments that access to CrossMAb technology eliminated the need for “mixing two different antibody molecules,” letting the team produce their candidate molecules more reliably. pRED’s expertise in how to apply CrossMAb technology and at the same time optimise the antibody constant Fc region (the ‘tail’ region of an antibody that facilitates part of its interaction with our immune systems) gave the team an edge for developing unique antibodies that could be used in new indications throughout the body.

Even with a solid antibody candidate and the ability to produce it reliably, successful passage through a rigorous clinical trials programme remains a challenge, especially for antibodies in a novel disease area. Matthias Rüth highlights the team’s “proactiveness of running experiments at risk” and their “creativity” in designing study protocols “for an unknown disease area”.  Sascha Fauser, Global Head of Ophthalmology, highlights that, at this stage, the team continues to “follow the science with the kind of determination and commitment that can move mountains.”

Scientists live for when a goal is achieved, and their tireless efforts in the lab translate into positive clinical evidence. The scientists clearly remember when they heard of the positive Proof of Concept in the clinic, which does not happen too often, as you can imagine, and is the biggest reward for researchers.

With their shared passion, access to the latest technology, and diverse culture, the scientists of Roche pRED are exceptional at driving innovation and taking antibodies to new disease areas. With the patient at the heart of all we do, pRED is strongly science-driven, which enables us to adopt unconventional ways of thinking, having a breakthrough-mindset to pursue a very good idea further. While there will always be a new challenge to summit, the team at Roche pRED will always be ready to reach for the highest point!