It’s time for our new mini-series on a key topic of interest. In this post we take a look at interesting data we came across at ASCO relating to the innate immune system… what’s important here is exploring different ways of jumpstarting the immune system using various approaches. These can range from cytokines to Toll-like receptors (TLRs) and involve both small cap biotechs and big Pharma alike.
There were quite a few examples to be seen and heard in Chicago, something that researchers turned out to be quite enthusiastic and passionate about too, as we learned from numerous interviews.
Dr Adi Diab at the Idera TLR9 poster #ASCO18
This niche is both early, as well as up and coming for many outsiders, although some of the approaches described we first started covering and writing about back in 2015, so regular BSB readers will not be unfamiliar with the concepts.
It’s always good to follow targets and companies over time from preclinical to clinical development and see how the proof of concept stands up to scrutiny. Sometimes though, it’s about finding the right combination partner or patient subset and… boom. Other times researchers need to do additional work to figure out the optimal approach or schedule. There’s no formula for success and the path forward can be one that’s well worn or less well travelled.
Add on top of this ridiculous hype and expectations and you get a recipe for disasters and pratfalls pitfalls along the way. Oncology R&D is a roller coaster, after all.
In the first post of our series, we begin with TLR9 and some encouraging early data with this approach. We explore the data generated through the lens of an investigator in one of the trials and what he and his patients have experienced, which makes for interesting reading.
To be clear, this is quite different from the disappointing results seen in the past with motolimod (VTX–2337), a TLR8 molecule…
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As we demonstrated in the recent Novel Targets podcast that opened Season 3, one topic that is a key focus for many in the IO space is addressing mechanisms of immune escape and acquired resistance to single agent treatment with immunotherapy.
We’ve seen several oncogenic escape mechanisms reported, included activation of the JAK/STAT pathways in some patients and loss of existing immunity when the tumour suddenly becomes cold or an immune dessert.
The good news is that there are a number of ideas that can be pursued, including activating the innate immune system in various combinations.
As we see more companies invest in the innate immunity space in order to have a rational partner with which to combine with their checkpoint inhibitor, it will be important to maintain focus on trial designs and synergistic mechanism of actions to improve efficacy while reducing the potential for overlapping or severe toxicities.
Here’s one intriguing and promising new approach that caught our eye this month that is worthy of researching and following over time…
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Having heard about a one day symposium on immunotherapy organised by Charles River, I headed over to Munich and the EORTC-NCI-AACR conference a day early… Providentially it seems, as the Lufthansa strike will likely affect a few travellers en route to the Triple and ASH/WCLC/SABCS conferences.
The focus of this excellent one day event was on ‘Mapping the future of cancer drug discovery.’
So what stood out as interesting and intriguing?
Quite a few things, as it turned out, including a novel target in cancer research that I haven’t come across before.
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National Harbor, MD
Despite remarkable results with cancer immunotherapy to date, we do need to keep out feet on the ground and remember that response rates are relatively low to modest (10–30%) and the majority of patients do not respond or see a benefit with these approaches.
As we start moving beyond checkpoint monotherapy, the realisation has fast hit many researchers and companies that we really don’t know as much about the tumour microenvironment (TME) as we would like.
No doubt we will learn a lot more about it from the combinatory approaches, but be aware that this also means higher risk associated with such developments – we will likely see a lot of failures – and hopefully, some successes too.
This is where the little biotech companies have an opportunity to shine… they may have some intriguing IO compounds in development but not an anti-PD1/L1 backbone, meaning they can collaborate with a big pharma company to explore novel combinations in small phase 1/2 trials to determine what works or not. This is much lower risk (and R&D costs) for both parties and we get to see more quickly where things shake out.
At the annual Society for Immunotherapy of Cancer (SITC) meeting last week, there was a whole day devoted to New Immunotherapy Drug Development.
Some of these agents look worthy of watching out for and following their progress. A variety of data in different targets and MOA were presented from big and small companies alike. We selected a few of the promising ones for further review and discussion.
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