Remember the good old days at ESMO17 in Madrid? Sadly there’s no face to face networking at this year’s ESMO20 virtual meeting!
In this third ESMO 2020 Preview the focus is on early stage immunotherapies – we’ll cover targeted therapies in a separate review article.
As new regimens evolve involving multiple immune targets, this complexity brings with it a greater need to understand cell-cell interactions – not just immune cell relationships, but also oncogenic, metabolic, and even epigenetic ones. How do they all fit together and what happens when we interfere with those relationships therapeutically?
Often the simple answer is we don’t know until we head into the clinic, I’m afraid.
Beyond the obvious phase 3 IO readouts in the various Presidential symposia and Proffered oral sessions there are quite a few emerging ideas – old ones with a twist as well as entirely new ones – which we can consider and discuss.
Here, we highlight five key IO areas related to cancer immunotherapy and explore the various concepts as preparation for the upcoming meeting…
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Yesterday, we started the first of a multi-part mini series on STING agonism with a quick look at the broad landscape and some of the competitors in this space, which has definitely grown over the last four years since we first wrote about the STING/cGAS pathway.
In the latest part of the STING series, we talk to a small, privately held biotech who are developing a slightly different approach to the first generation agonists currently in early phase clinical trials.
One goal that many are looking at with STING agonism is to try and take less inflamed tumours and turn them into inflamed ones (or cold to hot in layman’s parlance).
We also need strategies for adding those middling tumours that are neither purely inflamed nor non-inflamed i.e. immune excluded and may have other factors influencing their tumour microenvironment, which is something else we also discuss in the interview.
No one would ever describe the trials and tribulations of oncology R&D as a cakewalk, there are certainly plenty of challenges to address on the discovery, preclinical, and even clinical front before we even get to consider the financial need to raise money, pharma collaborations and (hopefully), eventual commercialisation post approval. It can be a wild roller coaster ride at the best of times.
We have an agnostic approach to cancer drug development and cover small and large companies in equal measure.
So what can we learn from the first of the next generation STING agonist companies?
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We first wrote about this innate pathway back in early 2015 – before it became famous and controversial – when things seemed much simpler then.
Imagine the basic concept… add an immune agonist – this targets the innate immune system to jumpstart or wake up the immune system in colder tumours – to an established adaptive immune therapy such as checkpoint blockade and see whether any magic happens. In practice, this turned out to be much easier said than done, because in reality mouse and man have quite different immune systems and do not react in the exactly same way, which makes extrapolation from one to the other challenging at the best of times.
Still, back in 2015 there were barely a handful of STING agonists that anyone could really put a name too, now there’s 18 compounds in early pipelines and counting.
Not all the players are small biotechs either, as big Pharma is certainly paying attention to the smaller biotechs (both private and public) generating molecules, especially now that early clinical data (alone and in combination) is beginning to dribble out.
Aside from collaborations and licensing deals, there’s also an increase in patents in this niche, which is often a sign of competitive activity.
Four years on, how has the landscape changed, what does the data look like and what sort of issues need to be addressed?
In the first of our latest three-part mini series, we look at the competitive landscape and how it has changed (quite drastically since 2015, I can assure you!). In parts two and three, we look at two different up and coming players in the STING space with very different approaches.
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