It’s time for an update on TLRs – Toll-like receptors – as a way of igniting the fire of the tumour microenvironment. We have repeatedly seen how only a minority of patients respond to immune checkpoint blockade and how there are a multitude of reasons for why this is the case.
In some patients, the immune response is stalled in some way, thereby necessitating a jumpstart. Reasons for this might include lack of recognition of the cancer cells, poor antigen presentation, immunosuppression, immune escape and so on.
In other words, we need more firepower and novel rational combination approaches to stimulating both the innate and the adaptive immune systems in order to derive a more potent and durable response in a larger number of patients. That’s where TLR agonists come in.
As always in oncology R&D, there have been some failures already but we have also seen more promising compounds emerge as well as improved understanding of the science behind the immune system defects that occur in cancer.
Armed with this knowledge, will the current crop of molecules produce better results? To find out, we took at look at some of the recently available data and also interviewed an emerging new company in this niche to learn more about their quite different approach to the challenges…
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At Biotech Strategy, we’re fans of science-driven companies, and one that we’ve been keen following for over three years now is Nektar Therapeutics (NASDAQ: NKTR).
Drs Jonathan Zalevsky and Adi Diab
We last spoke with the “dynamic duo” Nektar’s Dr Jonathan Zalevsky (CSO) and Principal Investigator, Dr Adi Diab (MD Anderson), back at SITC17.
Since then, much noise and attention has focused on cytokines and the potential they have to improve responses with checkpoint blockade. There are plenty of sceptics out there who don’t believe they add anything in combination, while others are equally adamant that they do.
It was a pleasure to catch up with them again at ASCO 2018, and in this post we take a closer look at what the NKTR–214 data presented in Chicago does in fact tell us.
Is it hype over hope, or is it the real deal?
What did we learn about NKTR–214 at ASCO18 and how should we interpret this data from a clinical and scientific perspective?
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We’re at a crossroads in the IO space, where much of the low hanging fruit has been already plucked and now we could be in limbo for the next 2–5 years while we wait to see which of the IO-IO or IO-other combos pan out as winners.
Part of the problem is that we don’t yet know all the potential mechanisms of resistance or immune escape involved, so imagine figuring out how best to optimally modulate the tumour microenvironment on top is going to be challenging – each tumour type is heterogeneous and highly complex.
In addition, the field has heavily skewed towards obsessing almost exclusively over T cells, which may or may not be a good thing. There are alternative approaches that are starting to generate interest and results.
As Andrew Shepherd, the fictitious leader of the free world in the American President famously said:
“We have serious problems to solve, and we need serious people to solve them.”
One promising company in this space is Nektar Therapeutics. At SITC this week they had some elegant and intriguing early data that combined an innate immunotherapy approach with checkpoint blockade. We have been following their progress for a while now and it’s a great time for an update!
Dr Adi Diab NKTR-214 #SITC2017
Here we explore the data and have our latest expert interview that is not merely a couple of paragraphs long with a few platitudes or topline quotes… this is, quite frankly, a comprehensive review and strategic roadmap of what Nektar Therapeutics are doing in the IO space, why they are doing things a certain way, and where they are headed – in their own words…
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