Finding pathways to success in breast cancer
The last week brough a huge tsunami of data across varied topics ranging from hematologic malignancies (ASH), breast cancer (SABCS) and immunotherapies (ESMO IO) – we’re still digging our way out of it all!
There’s plenty of detailed analyses yet to come from all of these meetings, including some KOL interviews and thought provoking pieces to consider as well.
Here we look at some translational findings from academic researchers as well as companies involved in clinical trials in breast cancer. Yes, it’s time for some post SABCS reviews on a series of different topics…
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National Harbor – Missing the Fall colours!
As we get into the final swing of the Fall cancer conference season, at SITC this weekend there was much to think about in terms of early stage oncology drug development.
Still, it did feel rather surreal not to be in Maryland at the Gaylord National Centre in National Harbor for a live meeting this year, especially considering this particular specialist IO meeting tends to be held in a small jam-packed hall with nary an empty seat to be had!
I thought it would be fun to focus on an area which is slowly receiving more attention, with at least one sub category actually beginning to look quite promising indeed…
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It is becoming increasing obvious in these challenging times as the pandemic spreads globally that no corner of the earth (except perhaps the Antartica) is being left untouched. As lockdowns begin or continue depending the phase the spread is at, this also has numerous implications for clinical trials, both academic and company funded studies alike.
Which direction should we be considering for early anti-cancer therapeutics?
One of the broader effects of the coronavirus pandemic likely means we won’t see much new data on many of the clinical trials after the currently scheduled presentations for AACR, ASCO, ESMO and ASH for a while yet, perhaps well in to 2021, which in turn is a strong reminder if we want to see how much progress is being made then we need to look at what data is available now.
I can well imagine many folks are already completely Zoomed or WebExed out from constant online meetings dealing with the implications of the pandemic on research and clinical development, as well as what happens to new and existing trials, so the idea of listening to two days of a virtual meeting on top is probably a bit daunting for the time-challenged observers amongst you.
AACR’s virtual meeting is a wonderful opportunity for smart folks to take some careful snapshots of where we are now, and how some of the early pipeline agents are shaping up.
The good news is we while your online internal meetings continue apace, we will be posting many reviews, summaries, discussion and analysis of the data here on BSB, hopefully sparing many of the additional stress in busy times. We plan to make the process of analysis and commentary relatively easy so you can follow along with us.
For reference, you can access all of our ongoing AACR20 conference coverage here. Future posts will also be added to this magazine page as they are posted.
In our fourth AACR Preview series, we take a keen look at some additional early products in development of interest, as we continue our updates on the never ending oncology R&D journey.
We highlight 10 emerging agents in early stage development to watch out for…some are new and others we previously reviewed preclinically and have moved along in their R&D journey into the clinic, with good and bad results to think about.
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National Harbor, MD
With the abstract drop from the 2019 Society for the Immunotherapy of Cancer (SITC) meeting now available, what can we learn from some of the research slated for formal oral presentation this year?
Here in part one (posters will be reviewed tomorrow) we take a look at a mix of preclinical and early clinical studies that grabbed our initial interest from the oral presentations – they include the good, bad, and intriguing – to see exactly what can be learned from this year’s mix of abstracts?
The short answer is quite a lot.
Every year the what to watch out for preview is a popular one. This year there are some surprises in store as well as some particularly important findings that BSB readers may well be keen to find out more about ahead of the conference later this week in order to maximise their thinking and avoid the inevitable brain-fry and fatigue that sets in on Saturday afternoon…
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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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Unlike last year, rain in San Francisco wasn’t a feature in 2019
If there’s anyone who hasn’t got fed up looking for somewhere to sit and chat or have a meeting in San Francisco at the 2019 JP Morgan Healthcare conference this week, then don’t be surprised…
With meeting space continually at a premium and many attendees unwilling to pay exhorbitant table rental prices, you now see people resorting to the lobby steps at the Sir Francis Drake, while the ladies have the advantage over the gents of access to the powder room in the Westin (with plugs!)
There’s also a movement from the chic to the shabby:
JPM is as much about informal meetings, pitches and confabs about new ideas, as it is about the actual CEO presentations, and so this situation is likely to continue in future years.
Meanwhile, we continue to dive in with our latest daily blog and put a bunch of companies through their paces. If day 1 is all about the big pharmas, by day 3 the focus is much more on up and coming or mid sized biotechs…
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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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San Francisco: In the final post of the week, it’s time to focus on some of the interesting concepts and early ideas being explored in GI tumours such as pancreatic and colorectal carcinomas.
Gems from the Poster Hall or what Dog Drug Heaven really looks like?
Despite the image implied by the used poster bins (right), there were actually several encouraging signs from emerging IO approaches as well as some surprising results that lead to some compounds – or at least some indications – going off to dog drug heaven.
There were also some salutory lessons to be learned in terms of understanding biomarkers and useful these can be.
After years of incremental improvements with targeted therapies, it’s time to look at whether some immunotherapy combinations can make an impact in what is known as cold tumours.
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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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