Immuno-oncology (IO) has transformed our approach to treating cancer, ushering in a vast range of drug development opportunities. Despite this, many companies struggle to capitalise on the huge potential of this field. This is because IO raises unique developmental challenges, such as predicting immune cell function in the complex environment of an evolving tumour, and encouraging more potent antigenic stimulation. Even if they overcome these hurdles, drug developers also face significant commercial pressure as the research and development landscape is becoming increasingly crowded.
To successfully navigate these challenges, you’ll need access to significant experience across a whole range of disciplines. In particular, you’ll require a combination of commercial, clinical and scientific expertise – which can be difficult to come by. In this blog we highlight some of the areas where an in-depth understanding of IO drug discovery can be particularly valuable, and discuss how you can use this expertise to plan a successful programme.
You’ll need commercial expertise to define your niche in immuno-oncology drug discovery
Before starting your programme, you will need to be able to demonstrate good market awareness –as for your drug to be successful it needs to show a clear therapeutic or commercial benefit over current treatments. Therefore, when you’re planning your IO drug discovery programme, it’s important to consider the potential competition – not only what’s currently licensed, but what could be licensed by the time your therapy is approved.
However, developing a clear picture of the landscape is a complex and time-consuming task, which can be difficult for a full-time scientist to fit in alongside other commitments. What’s more, it can be difficult to keep on top of the latest developments, as the marketplace is rapidly evolving. In fact, with research in this area progressing at an unprecedented pace, some areas of the pipeline are now incredibly crowded. For example, landscape analysis in September 2018 revealed that while 417 targets are under investigation in IO, half of the agents in development concentrate on only 48 of these targets.
This illustrates the significant competitive pressure in this field, but also highlights the potential for novel opportunities to investigate the less-studied targets. As such, with a detailed awareness of the market, you’ll be best placed to select your targets to maximise your chance of commercial success.
Ultimately, whichever target you choose, it’s critical that you design your programme to take an efficient path through discovery and development. To achieve this, you’ll have to couple your market awareness with a detailed understanding of multiple scientific disciplines. One of the key elements you’ll need to incorporate in your programme is specialist immunological expertise.
Immunological expertise is essential for target validation in IO drug discovery
A thorough knowledge of immunology is vital to optimise your path to the clinic. This is because you’ll need to understand how your target is expressed across a range of cancers before you can decide which patient population to focus on. It’s crucial to choose a specific patient group early on in your programme, so that you can take its tumour biology and particular needs into account when you’re planning your preclinical phase. In this way, you’ll be able to ensure that all your preclinical studies are designed to support your clinical trials.
At the top-level, this sounds relatively simple, however, understanding the expression of your target can be a significant challenge in IO for a number of reasons. Firstly, the tumour micro-environment is incredibly complex, containing a whole host of immunosuppressive signals coming from tumour cells, stromal cells and different immune cell populations. To complicate matters further, immune cells show significant functional plasticity. In fact, there’s a high chance that your target could be expressed in multiple immune cell populations, potentially with different downstream effects.
Given these intricacies, it can be incredibly valuable to engage with highly experienced immunologists early on. By leveraging their specialist scientific guidance, you’ll be well-placed to characterise your target’s expression in appropriate target validation studies.
In particular, immunologists will be able to advise you on the most appropriate sample materials, tools and techniques to use in these studies. There are several techniques you may wish to employ here: while histology will remain the workhorse for tumour analysis, you can also benefit from additional tools for target validation. For example, Nanostring’s cancer immunology panel can provide you with large amounts of transcriptional information. While this doesn’t identify the cellular source of individual mRNA, you can gain this information by using RNAscope in combination with immunofluorescence.
By having the in-depth expertise required to collect comprehensive validation data and to interpret your information appropriately, you’ll be well-equipped to take an efficient path through IO drug discovery and development.
Clinical expertise is vital in immuno-oncology to help you understand your patient population
Employing clinical knowledge from early on will significantly improve your likelihood of success in IO drug discovery and development. By understanding the clinical environment from the start of your programme, you’ll be well-placed to develop the most relevant preclinical development plan for your compound.
However, if you don’t take the clinic into account from the outset, you run the risk of wasting time and resources collecting data that won’t support appropriate clinical trials. For example, you could reach the stage of proposing a clinical development package, to be told by oncologists that your dosing regime has no chance of achieving patient compliance for a clinical trial. In this situation, you may have to go right back to the drawing board and create a new formulation that can be used in a more appropriate dosing regimen.
To avoid these pitfalls, it’s essential that you interact with clinicians from the very start of your programme. With their advice, you’ll be able to make well-informed decisions regarding your patient population from the outset. In fact, with this proactive approach you can define the design of the clinical trials you’re aiming for early on, then plan a streamlined preclinical phase to support these studies.
Combining multiple areas of expertise to optimise immuno-oncology drug discovery
By combining a thorough knowledge of the relevant commercial, clinical and immunological landscapes, you’ll be best placed to plan a streamlined and successful IO drug discovery and development programme. Ultimately, from the insights you gain, you’ll be able to define your indication and patient population early on, so that you can ensure that your preclinical studies are geared to optimise your path to the clinic.
Gaining access to the relevant expertise is critical in IO drug discovery, but it’s only one of five tips we’ve developed to boost success in this challenging field. If you’d like to learn about the other four strategies, download your free eBook: “Immuno-oncology: Five Tactics to enhance your Drug Development Strategy.”