Episode 9: De-risking Drug Development

Where There’s A Risk, There’s A Way: De-risking Drug Development at the Earliest Stages

Lonza’s wide array of analytical tools and professional experience create a go-to solution for small biotechs looking to decrease risk in their drug development process.

An evolving toolbox of technology and advanced scientific knowledge is fueling the growth of a wide range of next-generation drugs in today’s pipelines. These novel but complex products, while offering the ability to treat previously unmet medical needs across the globe, also present many challenges. This is often due to their unique profiles that require bespoke development and manufacturing processes as opposed to using well-known platform approaches, adding even more risk to a space fraught with uncertainty. This increasingly competitive market leaves little room for error or delay. Therefore, selecting and optimizing the right lead candidate becomes critical, as this allows you to de-risk your drug development process and maximize your chances of success.

The largest cause of failure during drug development is most often related to safety and efficacy, so it is important to have processes in place that can identify potential issues as early as possible. Simple, cost-effective in silico and in vitro assessments can help look at potential developability challenges  in the earliest stages and allow for modifications to the drug candidate and its process development to mitigate potential efficacy, safety or manufacturability risks.

Many of the drugs currently in early development around the world are initially developed by small biotechs, companies that often require the support of service providers to assist and to accelerate the de-risking of their candidates This is where Lonza’s Early Development experts step in. Today’s guest is Raymond Donninger, Senir Director of Commercial Development for Lonza’s Early Development Services in Cambridge.

To start the de-risking process, the team can predict development issues very early, based on the candidate’s sequence and structure. This knowledge allows for modifications to the drug candidate and its process development to mitigate risk early and increase the likelihood of a successful first-in-human study. The experts then also apply in vitro tools to look at developability challenges  and to mitigate potential efficacy, safety or manufacturability risks.

Curious to Know More?

We previously addressed the importance of immunogenicity in decreasing risk in drug production in Episode 5. To take an even deeper dive into the whole process, listen to the conversation between Martina Hestericová and Raymond Donninger, the Senior Director of Commercial Development for Lonza’s Early Development Services.

 

KEY TERMS in Context:

In silico immunogenicity and human cell in vitro assays are two essential ways to de-risk a molecule’s development pathway . In silico tests run computer models to predict a molecule’s interaction with the human immune system; in vitro testing assesses the molecule’s interaction with human immune cells.

The attrition of a drug candidate occurs when it reaches clinical trials but fails for one reason or another. According to Donninger, an attrition rate of nine out of ten candidates has remained stubbornly high over the years.

Attrition happens when a molecule has therapeutic potential but safety, target engagement or developability (for example complex, uneconomic manufacturing processes)  issues prevent the product from reaching the market. The de-risking process aims to reduce attrition to improve the chances for viable and safe therapies to make it to market.

According to Donninger, a T-cell epitope is a sequence within the protein that has the potential to allow the immune system to recognize it as being foreign and then mount an unwanted and potentially dangerous immune response. To learn more about de-risking and immunogenicity, listen to this season’s Episode Five.