Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘Pancreatic Cancer’

A oncology biotech to pay attention to

We are still on a quest – a patient journey, if you like – to find new agents capable of addressing the inherent issue of why do some patient’s tumours lack immune infiltrate and how do we go about fixing it?

Chihuly Glass sculptures always remind me of upregulating MHC

Over the last decade on BSB we have explored a veritable telephone directory of immune agonists, cancer vaccines, cytokines, bispecific and trispecific antibodies, additional inhibitory checkpoints, oncolytic viruses, small molecules, chemotherapy, CAR-T cell therapies, and various others.

Few have got the job well done in advanced solid tumours. Once MHC is downregulated, it becomes much harder to generate an immune response.

Stop and think about this for a moment.

It’s been a long slog to find the next big thing and a frustrating one at that for cancer researchers slaving away at the coal face. A lot of promising agents have come and gone – some quietly, others loudly – to end up in what Dr Patricia LoRosso wittily described as ‘dog drug heaven’. It is also dispiriting to write about so many ending in failure.

The good news is there are some new signs of life coming through, although it’s too early to declare a spring rennaisance. Over the next couple of weeks we’re going to highlight a number of young biotechs with encouraging or fresh ideas being explored in the clinic.

I also don’t want to raise too many hopes – especially as I have long been sceptical about some approaches with all their breathless hype – but here’s something to keep an eye on with an open mind because if it holds up where others failed then the company could be on to something…

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How to Knock Out Cancer’s Backup Plan

Boston Commons in the Fall

Cancer’s got moves… sneaky moves to ensure its survival when you throw targeted therapies its way.

Monotherapy whacks just one piece of the beast. Crafty tumour cells can simply switch on alternate pathways to drive growth again. It’s like a hydraulic game of Whac-A-Mole.

But what if you could outsmart cancer’s backup systems? Shut down its escape route for a while longer?

New preclinical data reveal a smart 1-2 punch that can trap tumours in a corner. The sweet science of vertical and cross pathway inhibition.

This new technique tags both early and late players in pathways like MAPK and PI3K/mTOR. When this happens, cancer’s got no fallback. Nowhere to run, nowhere to hide.

Tumours take a sustained beating with every line of therapy thrown at them. Signalling disrupted. Proliferation caged. Apoptosis triggered. TKO.

Combinations tested in NSCLC, RCC, CRC and pancreatic cancer. Impressive, durable regressions.  Researchers now poised to take this clever combo into the human ring.

Want the insider details? A ringside seat to the science? Step this way and we’ll walk you through the preclinical data blow-by-blow…

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Sotorasib impresses unexpectedly in pancreatic cancer

It’s time to go through the keyhole and take a look at progress with the KRASG12C inhibitors beyond lung cancer.

Years ago, there really wasn’t much hope in pancreatic cancer – it was an area big Pharma avoided because just about nothing worked well.  But those were the days of chemotherapy and promiscuous dirty kinases akin to a blunderbuss approach.

As we learn more about the biology of the disease and develop more selective inhibitors against oncogenes known to be active, have things improved at all?

In our latest cancer conference Preview, we pivot from a cell therapy meeting to the ASCO plenary series and take a look at how Amgen’s sotorasib is doing outside of lung cancer, an area where Mirati’s adagrasib was thought by some to have an advantage.

It’s always tricky to make judgment calls on the basis of a few patients in a catch all phase 1 trial – sometimes it’s better to wait until there’s a larger sample in a given cohort before rushing to declare winners and losers.

Often though, the data is something of a kaleidoscope – it depends on which angle or lens you view the data from.

In this post we include some expert reaction and commentary too…

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Important changes to watch out for in the GI cancer landscape

It’s that time of year when the ASCO GI and GU Symposiums come around, with GI up on deck first.

End of a rocky road for some GI cancers

Finally, after what seems like positive trials being few and far between we have a veritable raft of them to highlight, mostly for good reasons instead of bemoaning yet another negative phase 3 study – exciting times!

There’s also some up and coming agents in earlier development to watch out for, as well as the potential for additional indications for established drugs already approved by Health Authorities – what’s not to like?

In our latest conference Preview, we highlight some important trials and discuss them in the context of what’s gone before them to evaluate whether they will make an impact – or not…

BSB subscribers can read up on our ongoing commentary and analysis from the ASCO GI symposium – you can either log-in or click to access the back story behind the latest innovations.

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New developments in the KRAS landscape

A look through the window at the evolving KRAS landscape

It’s time for an important update on the KRAS landscape and emerging opportunities in this niche.

I’ve mentioned this a few times, but the real kicker is going to come from rational combinations in different settings.  Those companies who figure these out will emerge a stronger player than their competitors who focus on monotherapy.

With this idea in mind it behooves us to be alert and aware of what’s going on in the broader landscape beyond selective KRAS inhibitors against certain mutants.

Here we discuss the latest findings from two such targets, each quite different and yet both could have important roles to play going forward…

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Controversial developments in pancreatic cancer

It’s the dog days of summer and time for some meaty controversy to read!

For the longest time there have been several cancer types which have been incredibly difficult to treat therapeutically.

Metastatic melanoma and non-small cell lung cancer (NSCLC) both used to be in this category, as did glioblastoma and advanced pancreatic ductal adenocarcinoma (PDAC).

We have made great strides in changing the face (and more importantly outcomes!) for people with both metastatic melanoma and lung cancer, so what’s happening on the pancreatic cancer front?

The last two years gave certainly thrown up a series of disappointing clinical trial readouts such as RESOLVE, HALO–301, CanStemIIIP, and SEQUIOA, for example, where in each and every case the findings favoured the control arm of gemcitabine plus nab-paclitaxel over the experimental arm in terms of improving survival.  Not one of them was able to raise the bar and show a significant improvement over standard therapy, which is pretty disappointing.

So what can be done to change the face of PDAC?

If we want to improve further then we need to go back to basics and enhance not only our understanding of the funadamental biological mechansisms and processes, but also the models we use to interrogate the systems involved.

In this post, we look at six key new areas of research in PDAC and explain what we’ve learned and why they matter if we are to see new therapeutic developments arise from the ashes of the past…

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The next wave of IO agents for combination therapies

Part of the next wave of early immuno-oncology agents are focused on addressing the tumour microenvironment and inhibitory factors that dampen down immune responses.

As we look at all the options available, there are a few obvious ones such as physical barriers and inhibitory cytokines or chemokines, but beyond that are a vast array of other potential targets we can aim at therapeutically.

We have covered quite a few of these already, but here’s a new one to add to the list.

One particular advantage is that because it is early in development, few competitors have cottoned on to the concept yet. First mover advantage can have quite a few benefits, after all.

Here’s an important question to consider in terms of oncology R&D – would you rather explore a blue ocean strategy or follow the lemmings off the cliff and be 14th to market in a highly competitive red ocean?

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A hidden gem in the KRAS niche

Attention on small molecule inhibitors – after being in the doldrums for a while – seem to be making a comeback over the last year with much attention focused on a few companies developing new selective agents in specialised niches.

Time for a KRAS spring clean!

One such space is KRAS inhibition. Not just in terms of direct or indirect inhibition, but also with regards to tackling acquired resistance mechanisms such as SHP2.  While there has been quite the frenzy over what Amgen, Mirati, Revolution Medicine and a few others are all doing, other companies are quietly getting on with the business of producing some nice work and will soon be ready for the off.

In our latest review we explore some of the factors involved, which companies will need to be concerned about going forward, especially in the context of future combination strategies.

In solid tumours, with targeted therapies the winners are not always the ones who reached the market first, but rather the crafty ones who optimise the combination strategies and become ingrained in protocols across multiple situations.

Here we look at one of the hidden gems in the KRAS space and explore what it does, why it’s important and how it might fit in.  We also include a company interview with a scientist who gets the broader implications…

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New developments in GI cancers from ASCO GI 2020

Are GI cancers still marooned on an island or are they catching up with other solid tumours in terms of progress?

San Francisco – In the past, whenever I posted updates on any of the GI cancers they attracted noticeably less attention than other solid tumours and rightly so, especially given the lack of new agents and compelling data. If the highlight of a meeting is debating the merits of left versus right side tumour responses or bolus versus infusional administration then the plot has kind of been lost in the morass of abstracts available.

This year, however, things are looking up with a tidy group of studies that have what I call ‘interestingness’ – in other words, results that will tempt us to look deeper rather than merely skim in the hope of something new and shiny.

This weekend in San Francisco saw some highlights (and also lowlights) in the form of new clinical data emerging from the 2020 ASCO GI conference. That means we’re due a review so let’s rock ’n roll though the important studies to see what stands out from the crowd…

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Will 2020 be an inflection year for Kura Oncology?

A wet gloomy day in San Francisco was brightened up by some small biotech talks

San Francisco – The other day I mentioned that we could expect some cross pollination across several recent conferences and this latest post on Kura Oncology is one such example of that genre.

We’ve been following their story longitudinally for a while now and with a lot suddenly going on, 2020 could well turn out to be an crucial year for the company.

There is no doubt they have been pursuing a very focused precision medicine approach with tipifarnib and executing nicely on that strategy so far, but as more indications and additional pipeline agents move into the clinic do the same principles still apply?

To find out, we interviewed a couple of their senior executives and discussed both current progress as well as where they are headed…

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