Biotech Strategy Blog

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

Posts tagged ‘colorectal cancer’

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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Reflections on ESMO22

Vive La France! 

Despite the raft of negative trials presented in Paris this year, it wasn’t all bad news, although for a while it certainly seemed this way with quite a few phase 3 trials missing their primary endpoints.

It’s time for our ESMO review where we highlight no less than 10 trials offering positive vibes and encouraging signals, particularly in early stage development.

So what were the standouts and why do they matter?

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No, no absolutely not!

When it comes to targeted therapies, far too many external observers do not ‘see’ beyond the pretty scenery.

There’s an old obvious yet wise fable down here in Florida, which is often applicable to early stage oncology drug development – if it looks, snaps, or waddles like an alligator, do not feed it for you will surely get bitten (badly).

In this post we take a careful look at the updated adagrasib data in colorectal cancer presented at ESMO21.

There’s a lot of nuance, subtlety and questions this trial so far has not answered, and that will need to be considered if you don’t want to run the risk of being bitten by the lurking alligators.

BSB subscribers can read more about the challenges in interpreting the adagrasib CRC data presented at this year’s ESMO congress – you can log-in or click to access our latest analysis.

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Gritting it out

It’s time to switch gears and talk about neoantigens again… we’ve been covering this niche since 2015, as you can see from the relevant magazine page.

Aside from today’s expert interview, there will be an important update coming at ESMO in the Fall so this is a good time to set the scene ahead of time.

In our latest discussion, we cover some of the AI/deep learning aspects of the technological developments with a view to how they connect with the clinical challenges and progress since they don’t obviously exist in isolation.

As always there are important lessons and learnings along the way, such is the roller coaster of R&D, especially in oncology…

BSB subscribers can learn more about our latest interview on how deep learning can be applied to the neoantigen niche – you can read all about it by logging in or click to access our ongoing oncology coverage.

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Tackling a hostile tumour microenvironment on multiple fronts

It’s time to talk about new developments in immunosuppression and some of the different ways in which companies are tackling the hostile tumour microenvironment.

Obviously there are many potential culprits from neutrophils, macrophages, myeloid derived suppressor cells (MDSCs), adenosine, Siglec–15, and TGFβ to mention a few. There are others to consider as well, as we discuss with our latest experts in the hotseat.

Over the next couple of posts we will be highlighting different pipeline agents, along with in-depth expert interviews to explore some intriguing early or emerging approaches. Some are in preclinical getting ready to enter the clinic, while others are already being evaluated in phase 1/2 studies.

In this example of the genre, we had fun catching up on a biotech we first talked to a couple of years ago about their fledgling pipeline. How is doing now and what are they up to?

BSB subscribers can read more on our latest look at a clinical stage biotech company active in the cancer immunosuppression space – you can log-in or click to access our ongoing oncology coverage.

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Shipping the KRAS line

For students of anti-cancer drug development and history there’s a really nice review paper just published on some of the lessons learned from targeting the RTK/RAS/MAPK pathway, including KRAS, from the lens of structural biology.

There are plenty of examples shared using crystallography, as well as some important highlights along the way. They also mention the SHP2 molecular glues, which launched a new era in this niche with a flurry of companies and novel compounds rushing to evaluate their sparkly new SHP2 inhibitors in various dose escalation and expansion trials.

We’ve been following this niche since NIBR scientists reported important preclinical results with their probe molecule (SHP099) an allosteric inhibitor, which changed how many looked at phosphatases – finally it was a druggable target!

Fast forward five years and this weekend we heard the results from the improved clinical stage compound, TNO155, in an initial clinical readout from Novartis coming on top of the early data from Revolution Medicines at AACR with their SHP2 inhibitor, RMC–4630.

What did we learn and where are the company going with their approach?

Following presentation on the dose escalation cohort at ASCO over the weekend we received a bunch of reader questions and had some of our own too, so some expert commentary is included from the sponsor of the trial, Novartis.

BSB subscribers can read more on our latest update regarding SHP2 and RAS addicted cancers – you can log-in or click to access our ongoing ASCO21 coverage.

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Using bacteria as a trojan horse to target oncogenes

Colon cancer cells Source: NCI Center for Cancer Research

We have covered a tremendous array of different modalities here at BSB from chemotherapies, targeted therapies, immunotherapies, encompassing cytotoxics, small molecules, antibodies, bispecifics, various conjugates, and even viral therapy approaches, but what about the potential for bacterial approaches having an impact in cancer research?

This is isn’t something we come across every day week and thus it piqued our interest.

If we want to start thinking about creative ways to hit hard to target oncogenes then maybe we need to think outside the box a bit with some bold ideas…

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Parallel lines: opportunities and challenges in GI cancers

This weekend saw a variety of updated data presentations roll out from ASCO GI – think of the wide range of tumour types encompassing gastric, colorectal, liver, biliary, and pancreatic cancers.

What stood out from the crowd and why?

What are the threads and connections which might hold things together?

And why does KRAS keep cropping up in unusual and unexpected places?

To learn more from our oncology analysis and get a heads up on the latest insights and analysis pertaining to cancer conference coverage, subscribers can log-in or you can click to gain access to BSB Premium Content.

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What can we learn from Mirati’s adagrasib in lung and other cancers?

What’s the elephant in the KRASi room?

It’s time to look at the latest update on KRAS mutation specific agents in clinical development as we turn the spotlight from the Amgen sotorasib data at ESMO to Mirati’s G12C selective agent, MRTX849, now known as adagrasib.

At the Targets meeting last year in Boston, Dr Pasi Jänne presented the initial findings from phase 1/1b the lung cancer cohort.  This time around we get to hear him provide an update on the combined phase 1/1b plus phase 2 results, plus there’s an additional presentation from Dr Melissa Johnson on the non-lung cancer cohort i.e. GI and other cancers.

Ahead of the presentation this morning (US east coast time), BSB caught up with Dr Jänne for his perspectives on the progress made and where things are headed in the near-term.  He offers a thoughtful and candid approach to tackling a hard to treat cancer subset with targeted therapy.

To learn more from our oncology analysis and get a heads up on the latest insights and commentary pertaining to the EORTC-NCI-AACR Triple meeting, subscribers can log-in or you can click to gain access to BSB Premium Content.

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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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