Biotech Strategy Blog

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

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Posts by MaverickNY

Exciting new developments in the KRAS space

Old Post Office, Barcelona

What started out as a short update from the recent EORTC-NCI-AACR (ENA / Triple Meeting) in Barcelona on new data in the KRAS niche turned out to be a much more in-depth review in light of the explosion of corporate interest in this area.

At this meeting several companies provided updates on compounds, which either recently entered the clinic or were imminent, including the very first KRAS G12D degrader to make it past IND enabling studies. We also saw initial data for many new drugs on the horizon, including some in discovery or preclinical development. There were definitely some gems to be found in the poster hall!

If you didn’t make it to Barcelona for what turned out to be one of the most informative Triple meetings of recent years then this piece is for you if you’re following the burgeoning KRAS space.

In this post we highlight and discuss various direct KRAS approaches, as well as indirect upstream (SHP2), downstream (MEK, ERK, and ULK), and even cross-stream (PI3K) targets of interest.  KRAS G12C inhibitors were just a start, while the future may well look quite different…

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The art and science of a novel immunotherapy for solid tumours

This week we have been following the latest preclinical early stage clinical data coming out of the EORTC-NCI-AACR ENA Triple meeting in the beautiful city of Barcelona in Spain.

One presentation in particular on the art and science of overcoming T cell exhaustion with an intriguing and novel immunotherapy approach caught our attention.

What’s special or different about this particular immunotherapy and why does it stand out from the increasingly very competitive IO crowd?

Curious to learn more?

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Targeting MYC – trick or treat?

Trick or Treat?

For the last two years we have head much about our ability to drug intractable targets, with KRAS G12C being the first to fall and other similar mutations now firmly in many companies sights.

What if we were to consider going beyond KRAS and targeting another of the four horsemen of the apocalypse?

The count is still out on TP53 and β-catenin, while MYC was long thought to be the scariest and most difficult to consider for numerous reasons.

We’re interrupting our SITC Preview series to switch horses and highlight some important developments coming out of Europe this week.

In this post we highlight several new preclinical and clinical developments relating to the MYC oncogene, which includes some candid expert commentary from an expert in the field…

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The duality and the dark side of biomarkers

Fall in Boston

Far too many cancer drugs end up being pursued for the wrong reasons in the wrong setting, which is a dreadful waste of time, money, and resources. The focus lately on speed has not helped matters either and yet companies often forget the first-in-class to market agent doesn’t guarantee best-in-class performance.

With the upcoming ENA and SITC meetings there will likely be a veritable smorgasbord of different immunotherapies being presented, not to mention a variety of new combinations or regimens to consider – how should we proceed in terms of thinking about the data coming out and which framework should we use to assess them?

In this post we offer some tips and perspective on how we should perhaps be thinking about outcome measures, and in particular the use of biomarkers, when it comes to interpreting the results from early phase clinical trials that will be presented at these meetings.

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On overcoming resistance to protein degraders

One of the questions we routinely think about at BSB and ask researchers is what are the mechanisms of resistance underlying the therapy they are evaluating in preclinical or clinical studies?

If you understand what these are from the get-go then you can better design rational combination trials to address them and improve outcomes rather than leave things to the vagaries of chance.

In this post, we’re looking at novel approaches researchers are thinking about in relation to resistance with protein degraders and what this may mean for cancer new product development.

Curious to learn more?  Then check out the post below…

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SITC Preview 2 – a look at novel and emerging IO targets

After a couple of years in the doldrums with a bunch of negative phase 3 readouts, I thought this was a good opportunity to sit back and reflect on the next tranche of targets and see what we can learn about them.

The answers were quite surprising when you look at the group as a whole because not everything is about the PD(L)1 – CTLA4 axis, thank goodness.

In the latest preview we explore five different categories and highlight mostly early and novel developments coming along from early stage biotech companies, which may be of interest to our eager readers..

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SITC22 Preview 1 – Looking under the hood

In their first of our annual SITC Preview series for 2022 we are going to be focusing on addressing a critical issue, which has long stumped many a researcher.

Fall in Boston

I’m not a bit fan of combining two agents just because that’s what any given company has in their pipeline and trying to justify some vague rationale of what might work. This is akin to throwing spaghetti or mud at the wall and hoping something will stick – it’s a rather basic, if not crude, way to proceed with clinical development and relies more on hope than reason for success.

What if we looked at the data available from patients tumours and learned from the information instead?

This sounds obvious, yet few actually attempt a deep dive on this critical endeavour.

The good news is some companies making progress and are seeking to address the underlying biology of what lies beneath – as these examples we have selected highlight nicely…

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Going beyond PARP1/2 inhibition with novel approaches

Immune cells and tumour cells can act like a changing kaleidoscope depending on the situation

While we have seen many studies on the mechanisms of primary and acquired resistance to small molecule inhibitors leading to rational combination therapies, our understanding of what’s going on under the hood in response to protein degradation or immunotherapies is much less certain.

In our latest post, we explore how these worlds are now starting to collide and how tumour behavior at the time of resistance can better inform translational studies as well as future clinical combinations.

While there have been numerous studies emerging on the dual IO-IO front, let’s not forget there are still many opportunities to explore synergies with small molecule agents to address mechanisms of resistance…

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Dawn of new directions for protein and glue degraders

Time for a new dawn

In order to identify opportunities for cancer new product development, you have to be able to identify early emerging trends.

Coupled with this is uncovering the science capable of challenging current thinking or conventional wisdom, while providing a useful solution to what has been an intractable problem or better still, offers a technology solution, which previously did not exist.

With these issues in mind, in this post we’re taking a look at some recent developments in the fast moving field of targeted protein degradation (TPD), highlighting early data we think are not only noteworthy, but also offer potential for clinical impact down the road.

If you’re interested in protein degraders and molecular glues, you can find all our relevant content in this niche grouped here.

Want to know where the field may potentially be going? Then this post, and the next one are for you.

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Fishing for Gems from the Poster Halls Part 1

Fishing for oncology new product gems

One of my favourite exercises at conferences is exploring new or emerging targets in the the poster halls, either in the context of preclinical or early phase 1 data.

Undoubtedly it often ends up as a bit of a fishing expedition – you have all the anticipation and excitement upfront and just as in real life, sometimes you go home empty when nothing bites as happened to a couple of guys I was watching fishing in the bayou last weekend!

Much to their frustration, the mullet gleefully jumped around them without going near.

Assessing early stage oncology pipeline development is a bit like this too.  After following this particular niche for a while, it was time to take stock with a new clinical readout available.

Did the data live up to expectations or not?

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