Biotech Strategy Blog

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

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Oper Wien

It’s time for our second post on WCLC22, which also happens to be on the hot KRAS G12C niche.

The first part analysing the sotorasib plus checkpoint combo was posted here for anyone who missed it.

This time around we’re going to explore different combinations and look at some of the fast-follower agents coming up on the rails.

After all, this is more than a two-horse race where the winner isn’t necessarily the first past the post, but rather the one either with the widest therapeutic window or who figures out the optimal combination partners.

Curious to learn more?  Check it out…

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Münze Österreich

The World Conference on Lung Cancer (WCLC) is underway in Vienna, and for those who arrived early, Friday was the hottest day of the year (37°C) so far!

Is the data at the meeting as hot as the summer weather?

Companies undertake drug development with the best of intentions, but there comes a moment in time where you have to take stock of what exactly is the data is telling you?

Did we experience an epiphany or turning point at WCLC for KRAS G12C inhibitors in lung cancer? Or is there still a way to be travelled on the road to Damascus?

In this latest post we take a look at some key data presented during the meeting and what it means for those in this space.

It’s a story we’ve been following for some time, and as always, there are nuances to be had, because it’s far from black or white…

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Whenever I think of ‘salad days’ – a Shakespearean expression referring to a youthful time, a period of carefree innocence and idealism – the idyllic Indian summer of 1976 comes to mind when the summer actually meant more than merely a few hours of sunshine for a couple of days in England, rather than days of rain and inclement weather cancelling much anticipated leisure events.

Of course, with warm lazy days one also remembers the opportunity for voracious reading, thinking, staring up watching the clouds while letting thoughts and ideas coalesce in the background.

Science is a bit like this too, coupled with great ideas coming out of asking pertinent big picture or provocative why and how questions.

There has been a crop of excellent research published this year including a nice batch of studies on a diverse range of cancer related topics, which may have important considerations for future pipeline development or novel combination studies.

Obviously one can’t write about them all, so we picked half a dozen to pique our readers interest…

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Degrading proteins, block by block

Our KRAS review last week included a lot of different inhibitor compounds (well over 30 of them), illustrating just how complex this niche is rapidly becoming, with only a brief mention of targeted protein degrader (TPD) compounds since these are much further behind their small molecule inhibitor counterparts.

Since then there’s been some more big picture talks or three about the TPD space, which are well worth discussing, as well as a flurry of relevant questions from BSB readers to be addressed.

Here we discuss the KRAS niche in the context of protein degraders and look at the promise and some of the inherent challenges faced…

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It seems astonishing to realise only a couple of years ago KRAS was considered undruggable intractable and here we are, not only with one drug approved, another filed and veritable long list of fast followers, but a whole ecosystem of different agents vying for a place at the table.

The wonderful news is we are starting to think more broadly about life beyond G12C mutations, not only with different combinatorial approaches, but also also in the context of how to tackle other related mutations as well.

Here, we wanted to explore the evolving universe more broadly and assess criticality as well as applicability – which agents might shine tomorrow if clinical data turn out positive?  The simple answer is more than you know.

So just who are the rising stars in this emerging landscape and what can we learn about them?

Be warned in advance – this is one of our longest and most comprehensive reviews on BSB with over 30 compounds highlighted in different guises, so grab a cup of Joe and be prepared to come with an open mind…

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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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We’ve written a lot on TIGIT as a cancer target going back to 2015 (see examples here) as we have followed the trials and tribulations of numerous developments in this niche longitudinally.

I’ve often wondered how people would have viewed results from anti-CTLA4 trials had anti-PD(L)1 therapies came first and not the other way around.  You just imagine the disappointment this might have induced given the way things panned out!

Not all anti-PD(L)1 agents have consistently demonstrated similar results – some have succeeded where others failed. Whether this was due to differences in trial designs, different patient populations, or other factors is often something of a mystery since there is still much we don’t know – the unknown unknowns – and how they can impact performance. If they are not accounted for in the baseline characteristics then differences in outcomes might well unwittingly be impacted from the get-go.

It was always going to be tough to add in another immunotherapy agent and shift the survival curves up and to the right, thereby impacting outcomes even further.

Should we be considering the recent top line tiragolumab readouts an indication of failed trials or something else?

In our latest analysis, we consider a number of pertinent factors and discuss how they can impact performance…

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One of the many challenges in the oncology space is seeing the bigger picture of how companies evolve their early stage pipelines.

For some, it’s a bit like taking a walk in the forest and not being able to see the wood from the trees – the targets chosen are rarely random, especially those involving collaborations.  There’s a reason for pursuing a given approach, particularly i it is intended to be employed in combination with an existing, approved therapy.

There are many choices out there and even those with the deepest pockets can’t have everything, so often I’m fascinated by the selections that are taken and how they might fit in.

In our latest company review, we talked to a big pharma company active in the immunotherapy niche and sought to explore the early stage agents they are developing in the context of future doublet and triplet combinations.

Why are they doing what they’re doing and how might their approach be differentiated from others?

To find out more, check out our latest expert interview, which has a few surprises in store…

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Can we scale new heights with next generation anti-cancer agents?

One of the fascinating things about ASCO is how early new product development readouts outside of ‘hot’ names (or stock tickers) can often be ignored, forgotten, or simply dismissed as me-toos with seemingly comparable data.

The thing is, two people can look at a mountain and see it differently, much like five blindfolded people might describe various aspects of an elephant based on their perceptions of what’s in front of them – imagine what a tail versus a trunk or ear might produce, for example.

This is also particularly true with targeted therapies, which are undergoing something of a renaissance of late.

In this post, we look at five targets (and tumour types) where we are seeing some solid progress either with single agent therapy or with combination approaches, some of which – be warned – are rather controversial…

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There’s no ASCO meeting without the Bean

There’s always a parable or two to be had at ASCO and this year was no different, especially in the breast cancer space where there were plenty of phase 2 and 3 trials to discuss as well as offer commentary on the various findings.

Not all of the results were standouts though, with some creating controversy in the process.

Here, we take a look at some examples and put them in context…

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