Biotech Strategy Blog

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

Posts tagged ‘lung cancer’

The Subtle Art of Bispecific Architecture

Chicago!

What if the secret to bispecific success isn’t just dual targeting, but getting the binding balance exactly right?

Could this contrarian binding strategy explain why ivonescimab shows consistent efficacy across tumour types, while some competitors may struggle with dose-limiting toxicities or confusing response curves?

With ASCO data revealing 100% severe toxicity rates for some agents versus minimal bleeding for others, the binding affinity may determine not just clinical outcomes, but which companies might capture this bispecific niche.

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Old lighthouse, new shore

Torre de Hercules on St Patrick’s Day

The Tower of Hercules in the Galician town of A Coruna has the unique distinction of being both the only Roman lighthouse – built between the reigns of Nero and Vespasian – and the oldest in operation in the world.

It also offers a handy analogy for one of those good old fashioned stories where out of the dark biotech gloom comes an unexpected raft of light.

In this example, we’re specifically exploring whether a twist on a modality can illuminate a new path for novel cancer treatment.

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Breathing fire into novel combinations

Dragon sculpture at ⁨Kiyomizu-dera Temple⁩, ⁨Kyoto

Cancer cells can exhibit a dynamic ability to change their identity in response to environmental pressures or treatments. This flexibility allows them to adapt by taking on different characteristics, enabling them to survive in challenging conditions.

A tumour cell that initially depends on a specific growth pathway can shift its traits to rely on alternative mechanisms when the pathway is blocked therapeutically.

Much as a magician can conjure up an illusion, the nifty cellular shift can contribute to resistance to cancer treatment.

In some cases, tumour cells may alter their surface markers or acquire features typical of another cell type, making them less susceptible to targeted therapies.

Understanding this behaviour – and the molecular underpinnings of the changes – is crucial for developing more effective strategies to counteract tumour evolution, escape, and resistance.

What if the targets also change in the process?

Ah, but what if we can adapt a treatment regimen to aim at the evolved targets, assuming we know what they are?  After all, if we put a blindfold on an archer then he likely won’t be able to see what and where the target is, whereas if they can see then the chances of success is much higher.

In our latest review we look at a number of targets and novel combinations based on key findings around the underlying molecular changes…

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Bridge over troubled waters at ASCO24

The devil as they say is in the detail and teasing out what oncology clinical trial data really means can be challenging for the best of us.

In this post we take a look at several trials  reported out at ASCO24 and consider some of the nuances around the data, in particular what cancer new product professionals may need to think about in order to have an informed opinion.

For some, the data is a bridge over troubled waters, while for others the results were perhaps a bridge too far…

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A new dawn or the sunsetting of cytokines?

Much has been written about cytokines over the last decade in terms of various ways of employing them systematically as cancer therapeutics.

There has been little success reported, however, beyond a small number of patients receiving high dose IL-2 in certain situations such as melanoma and renal cell carcinoma.

What if we take an orthoganal approach to the problem and explore different ways of delivering the desired effects?

Does this change the outcomes, and with it, our thinking?

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Digging deep for answers

Imagine walking through some delightful countryside or along the coastal headlands…

Suppose you are then informed somewhere in this vicinity is a small patch – just one – of bright purple thistles in full bloom and your job is to find them as quickly and expeditiously as possible.

This is one challenge facing Pharmaland on a daily basis and while it sounds easy in theory, it often is more time consuming to answer than many may realise, including analysts chasing their colour commentary.

Today’s story explains the problem and illustrates how it might be tackled…

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Will targeting KRAS G12D prove more successful than G12C?

Are scientists and observers taking a distorted fish eye view of the KRAS world?

I’ve often wondered if in putting so much focus on ripping the progress of the G12C inhibitors to shreds, people simply lose focus of the progress being made elsewhere especially with different, yet related targets.

Here we offer some emerging highlights on several fronts, some of which ought to be well worth watching out for and others perhaps not so much…

Curious to learn more?

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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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The long and winding road to success

Garden of the Gods

This post is about some of the trials and tribulations around oncology R&D and how we have gone from broad targeting of a particular process to honing in on what basically represents a novel target in a much more selective and precise fashion.

It’s a bit like the difference between a blunderbuss versus a sniper’s rifle – you can induce a scattered or a narrow effect, and hopefully reduce unwanted toxicities in the process too.

Targeting achilles heels and vulnerabilities in the cancer cells are not new, but figuring out novel synthetic lethal pairs could well be key in terms of a failed trial versus a successful one.  These days, more and more companies are abandoning the dreaded catch-all phase 1 polyglot trials – aka refractory advanced solid tumours – for ones based on a more rational approach dictated by the science and underlying biology.

I’m delighted to see this trend emerge and hope more will continue.  After all, if you have a targeted agent why treat it in a nihilistic and un-targeted fashion, subjecting patients who have absolutely no hope of responding to Compound X to unwanted toxicities, when they might well have a better shot at an entirely different approach?

Without much ado, it’s time to focus on the novel oncology target – and yes, there’s a couple of early frontrunners already…

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New trials and tribulations in drugging KRAS mutations

Is the ride going to be a thrilling long or disappointingly short one?

The KRAS niche continues to rattle on at an incredible pace with new findings, new trials, or even a new molecular entity (NME) coming along seemingly every month.

In this latest update on the landscape, we discuss some important new findings, as well as a novel agent to thing about in this space, which is quite different from what we have seen before.

To be clear – this doesn’t mean a novel approach doesn’t have any legs, nor that the latest science behind where we should be going with combinations is doomed.  Indeed, sometimes finding a balance is a bit akin to a highwire act.

The important thing is to focus on the learnings and determine where the field might be headed…

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