Biotech Strategy Blog

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

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Sometimes I wonder when we are faced with particularly difficult challenges in oncology – there are certainly plenty of these to go around – if people give up before they start and consider certain endeavours far too difficult and thus any emergent approaches are considered tilting at windmills.

What if we could isolate and define the problem more specifically, thereby identifying where new targets might lie and then go about designing ways to tackle them?

When we do this the problem at hand is much more specific and less amorphous.

Here, we highlight and explore a key topic likely to be lurking in many abstracts over the next week across both hematologic malignancies and solid tumours alike… it’s an important subject many will ignore at their peril.

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There are plenty of innovative and creative ideas coming to the fore in oncology R&D of late, many of which are quite different twists on what we currently have available.

Early oncology development is rarely plain sailing – some fly like the wind, others fall over

As Dr Dan Chen of Engenuity noted in his talk in the SITC22 preconference session on lessons learned from IO combinations, if we want to cut to the chase when looking at emerging agents then we need to ask ourselves whether any of the concepts are seeking to address the limitations of the current products, particularly those associated with either primary or secondary immune escape.

After all, repeating the same old, same old is probably not going to move the needle in any meaningful way.

In thinking about which biotechs to pick for the annual SITC review, I also asked myself a couple of additional provocative questions – how are they distinguished from the competition, and in what way are they particularly compelling?

We’ll discuss these as we go through the selections, which includes both some solid developments as well as others we ought to be much more wary of offering too much hype over hope…

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Spotting the Baubles amongst the Glitter

Readers in the UK who follow the BBC show ‘Strictly Come Dancing’ will know this Saturday night the show returns to the iconic Tower Ballroom in Blackpool.  All the contestants wanted to make it to this stage of the competition.

To put this analogy in context, an oncology equivalent might be the prestige of giving an oral presentation at a major medical meeting, it’s something you definitely remember and want to do!

There are many metaphors related to dancing that can apply to cancer research e.g. we’ve heard one leading researcher describe how immune cells and cancer cells ‘dance’ together.  As they say, it takes two to tango…

How new products ’embrace’ and interact with cancer cells, their receptors and binding sites can be key to therapeutic success. There are a variety of ways to do this, one of which can lead to cancer cell death via synthetic lethality, a concept we’ve covered extensively over many years going back to the emergence of PARP inhibitors in 2006.

In this post, we’re taking a closer look at an emerging biotech company, their drug discovery pipeline, and some innovative targets that may enable their new drugs to better ‘dance’ with cancer cells in a way that interrupts their routine, and ultimately, leads to their death.

Keep on dancing!

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One of the joys of oncology research is that it’s data driven, which means companies can quite clearly see how others have fared, and where the gaps and opportunities lie for new product development.

There is always the potential to unlock the gates to the “secret garden,” whether it be targeting a tumour type previously considered intractable, treating an unmet medical need where there are few or no effective therapies, or in the case of immuno-oncology, manipulating the tumour microenvironment in a way that leads to an improvement in the long tail of survival we’re all looking for.

In addition to improved outcomes, you also need a safety profile with a favourable benefit/risk ratio, where there aren’t intolerable or life changing side effects or an increased risk of death. Who said it was easy?

Innovation takes many forms, and in this post we’re looking at how one biotech company may have unlocked the key to a secret garden through the optimised design of their molecule.  As always, it’s early days although it’s good to see companies looking to solve hard problems because the easy low hanging fruit wins in immuno-oncology went a long time ago.

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Fall leaves in Boston

Autumn (or Fall for our American readers) is a time of cyclical renewal as old leaves die off and fall by the wayside to make way for new growth to emerge.

It’s the same process in oncology R&D pipelines too; by 4th quarter earnings reports we start to see Product X or Y being officially discontinued/abandoned, or sent off silently to dog drug heaven without even an epitaph to claim.

What about the promised new growth opportunities or targets?

Well there are various cancer conferences either happening now or coming up, which should offer plenty of signals for hope amongst SITC, EBCC, SABCS, ESMO IO, with ASH signing off the final coverage of the year.

In our latest report, we highlight some key presentations to watch out for not covered in the earlier SITC previews.  Some look encouraging already, while others – in all fairness – may have some unexpected question marks to consider…

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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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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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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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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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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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