Biotech Strategy Blog

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

Posts tagged ‘KRAS G12C’

New directions in drugging KRAS

Where are we headed in the KRAS niche? Who are the new emerging players?

One of the most fascinating and intense sessions at the AACR-NCI-EORTC conference this weekend centred around the KRAS niche.

I think for too long many observers have focused on only two companies developing selective inhibitors and yet it is clear we have much to do in terms of improving outcomes for the majority of patients since some will be resistant upfront and not respond at all, while others will develop resistance over time.

What then?

The good news is there is a wealth of novel approaches and also quite a few other companies active in this space, as well as next generation inhibitors also coming along.

Just as the odds-on favourite doesn’t always win the Grand National – there are drug equivalents of Becher’s Brook after all – what looked liked long shots to many a mere two years ago at TARGETS19, are now looking more encouraging.

There’s all to play for and so it’s time for us to offer some perspectives and insights on a raft of new developments in the KRAS niche…

BSB subscribers can read up on our latest commentary and analysis from the cancer conference season for our ongoing TRIPLE meeting coverage – you can log-in or click to access our latest analysis.

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Spotting the wood from the trees

It’s time to turn our attention to the annual AACR-NCI-EORTC international conference on molecular targets and cancer therapeutics, often dubbed simply as TARGETS or TRIPLE for many industry observers.

Spotting the wood from the trees

With the ongoing pandemic, this year’s meeting remains a virtual one and runs from today through Sunday.

There’s quite a lot of intriguing abstracts to cover this year so we kick off our coverage with a look at KRAS combinations.

While the single agent activity of both sotorasib and adagrasib has been encouraging in lung cancer with G12C mutations, the rest test was always going to be what combinations will emerge as winners in terms of overcoming primary or acquired resistance (the mechanisms might be different in each case) in order to improve outcomes further.

Any agent targeting the MAPK pathway will necessarily be challenging in combination with KRAS inhibitors due to toxicities, but are there other approaches or could we finesse the dosing/schedules more optimally?

Here we look at two such combination strategies to see how they are faring…

BSB subscribers can read up on our latest commentary and analysis from the cancer conference season as we begin our TRIPLE meeting coverage – you can log-in or click to access our latest analysis.

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When things fall apart

One of the things that struck me at this year’s ESMO conference was the sheer variety and richness of the data across multiple treatment modalities, tumour types and even new products coming through the pipeline to vie with established products for time and attention.

It’s also interesting to see what kind of questions readers have – it’s time for another mailbag session where we take reader questions and attempt to put some colour and context on the answers, as well as offer some predictions in some cases.

The current crop spanned a wide range of topics and issues from TKIs and DDR agents to immunotherapy, and not just checkpoint blockade either!  People specifically wanted to know about various targets and different modalities, including cell therapies.

So what’s on offer in the candy store today and were they substantial in nature or should we dismiss them as weak sugar pills?

BSB subscribers can read up on our latest discussion and analysis from the ESMO conference – you can log-in or click to access our latest analysis.

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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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ESMO21 Highlights from Day 1

Pathways to success – or not?

When it comes to oncology new product development there are always multiple factors to consider, from novel targets, new combinations, different tumour types or settings, biomarkers, to patient subsets and much more.

At ESMO this year the poster session provides a particularly rich resource of early stage trials involving fresh ideas or novel approaches to explore on both the translational and clinical fronts.

In our latest conference coverage we highlight a few noteworthy ones and also point out some of the important subtleties and nuances to be aware of, since they may have a key impact on future trial success.

What’s not to like?

BSB subscribers can read more on our latest update and commentary from the ESMO conference – you can log-in or click to access our latest review.

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Standing out from the crowd in lung cancer

What’s standing out from the crowd in lung cancer?

It seems hard to imagine only a few years ago lung cancer was still in the doldrums with various chemotherapy doublet and triplet regimens showing little or no benefit for people with small cell (SCLC) or non-small cell (NSCLC) lung cancer.

Fast forward and my, how things have changed today with a raft of targeted and immunotherapies making a real difference to many people’s lives!

In our latest discussion highligting important trial readouts and published data, we also offer some potential new developments which might be useful down the road…

BSB subscribers can read more on our latest update and commentary regarding lung cancer – you can log-in or click to access our latest analysis.

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A bridge to a broad and deep oncology pipeline

A decade ago Novartis and Genentech/Roche were all the rage in oncology with their small molecule, CAR-T cell therapies, and a myriad of antibody programs seemingly in the news every month then things went quiet as agents either successfully made it to market, or were dutifully dispatched to dog drug heaven.

In the meantime, other companies and various novel targets came to the fore such as various next generation agents in lung cancer, bispecific T cell engagers, KRAS inhibitors, and such like, while different companies and targets took on a new focus.

This doesn’t mean the big two aren’t active, more that they are replenishing and moving earlier compounds along and these can take a while to move through discovery and preclinical to phase 1 trials.  The bridge across the two is always kept busy in large pharmas, in both directions.

With this in mind, I was keen to catch up with Novartis to discuss their new early stage pipeline.  It’s both broad and deep, as you might expect, but what stands out and what’s something new to watch out for?

BSB subscribers can read more on our latest update regarding SHP2 and RAS addicted cancers as well as other early stage pipeline targets – you can log-in or click to access our latest expert interview.

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Highlights and lowlights from the ASCO21 data drop

It still feels really weird not to be heading off to Chicago O’Hare in a few weeks

Every year at ASCO we take a quick look at various trials which jump out from the first pass of the data once the abstracts become available then follow up with more in-depth previews later.

There are some winners and losers in this mix, as well as some hidden gems and informative analyses to think about.

So without further ado – what stood out this year for better or worse?

To learn more about our pre ASCO meeting analysis to can get a heads up on key oncology commentary and insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

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Digging deep on SHP2 and KRAS

A bright future ahead or early warning signs?

It’s time for another update on the KRAS and SHP2 niches… it seems this space is much faster moving than our previous quarterly rolling updates in the past on other areas such as T70M in EGFR mutant lung cancers, checkpoint blockade in NSCLC, or new developments in CAR-T or CLL/iNHL.

It’s a sign of the modern times.

There’s always new entrants, new science and new clinical data to learn more about so without much further ado, let’s roll…

To learn more about our ongoing reporting on the KRAS niche to get a heads up on key oncology commentary and insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

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Novel combination strategies to enhance KRAS inhibitors

A modular approach to bolting on different combination partners might be useful

In this second AACR 2021 Preview, we take a broad and deep look at the KRAS niche, with respect to both molecular glues (SHP2) and covalent inhibitors (G12C, RAS::SOS1 etc).

There’s a lot to cover here in terms of basic and translational science, as well as clinical learnings and also plenty of intricate interactions coming to the fore.

Where are we going – and just as importantly – shouldn’t be going with combinations? Not all of them will work out and not all combination partners are the same, which certainly adds to the spice and interest!  There’s the additional issue of which strategies might be useful yet haven’t been considered by the KRAS players.

Every time we look at this rapidly growing niche there is something new or important to discuss…

To learn more about the latest AACR21 data and get a heads up on our oncology commentary and insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

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