Biotech Strategy Blog

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

Posts tagged ‘lung cancer’

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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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…

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WCLC21 Preview of key data to watch out for

Time for some new directions in lung cancer?

It seems only a few months ago we covered WCLC20 and here we are again with another lung cancer conference.  This is because the pandemic certainly made an impact last year in more ways than one since the meeting was split into two, with the second half of the sessions being showcased in January.

This time around we highlight quite a few presentations on the IO and KRAS related pathway fronts, as well as some updates on various targeted therapies – with a few unexpected surprises in store.

There are also some important genomic and biomarker presentations to watch out for…

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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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A critical look at the Amgen sotorasib data in KRAS G12C mutated lung cancers

It feels weird to be covering the WCLC from Singapore remotely after remembering the rain in Spain at WCLC19!

If we look at the more mature phase 2 data now available for Amgen’s sotorasib (AMG 510) in KRAS G12C driven lung cancers, we learn there are quite a few nuances and subtleties at play. These aren’t always obvious in top line press releases or even in presentations until we consider the broader niche in which they are competing.

Amgen submitted the sotorasib applications to both the US and EMA health authorities in December.  With breakthrough designation status and clinical evidence of activity in an area of high unmet medical need, it’s hard to believe the approval won’t be forthcoming sooner rather than later, at least in the US.

Mirati is expected to showcase their phase 2 data later this year, so I would highly encourage people to hold off with cross-trial comparisons until we see how their more robust data look at the RP2D.

In the meantime, we can take a careful look at the latest Amgen data.  We do those not only from a BSB review but also through the lens of a company perspective and consider some of the key strategic issues we need to start thinking about…

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How will AI impact oncology R&D?

There is no doubt in my mind artificial intelligence (AI) has the power to improve cancer diagnosis because if the system is trained sufficiently then an algorithm should potentially be able to spot subtle patterns, which can be missed by the human eye. Even well trained pathologists are not infallible, after all, as we have seen in other areas of cancer research diagnostics relating to immunotherapy.

There are a number of benefits to using computers and machine learning, such as reduced error rates in diagnosis thereby limiting misdiagnosis, as well as increased precision in determining low versus high risk lesions, leading to appropriate clinical intervention rather than under or over treatment. There are other potential advantages too, including speeding up processing of thousands of scans in a screening and prevention study.

A couple of years ago I was fascinated by a Google study published in Nature Outlook, which explored the value of 3D deep learning in low dose computed tomography of the chest for the purposes of lung cancer screening. They proposed a deep learning algorithm using a patient’s current and prior computed tomography volumes to predict the risk of lung cancer. This was something they were able to accomplish with surprisingly high accuracy, even to the extent they could beat out half a dozen radiologists with absolute reductions in the rate of both false positives and negatives.

The ultimate value of this kind of analytical approach?

“While the vast majority of patients remain unscreened, we show the potential for deep learning models to increase the accuracy, consistency and adoption of lung cancer screening worldwide.”

This month brings a confluence of an specialist AACR meeting plus WCLC, which means there are some fresh ideas to learn from and also some emerging clinical data to consider…

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