Biotech Strategy Blog

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

Posts tagged ‘SHP2’

A saying for the ages from Albert Einstein

Oncology R&D is – perhaps surprisingly – very much like the bicycle analogy Albert Einstein described.

There are many ways we can see this happening at meetings such as AACR and ASCO as companies struggle to finesse the therapeutic window and balance efficacy with toxicity, for example.

Or how about finding creative ways to extend and broaden a particular drug class?

Another approach might be to take an entirely different angle to tackling a tumour type by targeting an antigen few others are pursuing. Just because the herd is going in one direction doesn’t mean you should follow them down the same path as well.

Then there’s switching modalities, orthosteric versus allosteric inhibitors, or how about some med chem magic where researchers seek to enhance the good properties and minimise the weaknesses while still hitting a target selectively?

All of these methods require some kind of balancing act if you want your pipeline to move forward rather remain still or fall over in the doldrums.

Today’s post has all of this and more – there are some novel compounds and targets, emerging biotechs and big pharmas, as well as innovative thinking to make a difference. Several of these agents are first-in-class, which means the rest of us can learn much from the lessons they have shared.

What’s not to like?

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A graceful white swan serving as an antidote the current COVID19 pandemic (black swan event)

In our the third of our AACR 2020 Preview series, we turn to the KRAS pathway to look at some new aspects, whether they be new targets, novel agents in development or even twists on the biology of the disease.

There’s quite a bit to discuss here, certainly more than I was expecting considering it was expected to be a down year by some after all the excitement of last year’s revelations and developments in the clinic!

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First in class or best in class?

Which paths will ultimately lead to success with novel targeted therapies?

Ah this question often seems a perennial one to consider at AACR annual meetings – and this year is no different in this respect.

Personally, to me, it doesn’t really matter what you claim aspirationally based on preclinical or even early phase 1 dose escalation data because… a lot can happen between then and later registrational studies.

Think about it carefully – weak efficacy, wrong tumour selection or setting, adverse event profiles, even narrow therapeutic windows can all too soon interfere and play havoc like a wrecking ball with many a well intended clinical program, especially once you start looking at combination strategies!

No, it’s not as easy as it looks sometimes.

In our latest AACR Preview series, we take a look at a number of targeted agents in development, many aimed at novel targets at are not run-of-the mill…

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As we continue to follow the emerging KRAS niche longitudinally, we can easily imagine the kind of roller coaster ride that ensues with new product development in oncology R&D.

Early last year we posted an interview with Mirati’s CEO, Dr Chuck Baum, discussing their selective KRASG12C inhibitor.  A year on much has happened in the intervening time – additional competitors and potential collaborators have entered the clinic, a few mechanisms of resistance identified, and numerous combination partners have been suggested.  The company have also aired their own phase 1 data and new trials are expected to open during 2020.

This time around we talk to both Dr Baum and the company’s CSO, Dr James Christensen, about their experiences in the front line in terms of translating the preclinical data into clinical trials, their thoughts on important scientific data as well as the competition, and what to watch out for going forward.

This field is going to not only go fast judging by the emerging research published to date, but it’s also going to get way more complicated than many observers realise.

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The calm before the storm as the KRAS competition heats up and also gets more complex in the process

I was very tempted to tease everyone and say something along the lines of… ‘while you were all partying, there was some new KRAS clinical data being presented somewhere in the world’ but that would be rather naughty, I suspect.

Instead, I’ll simply point out that it’s time to take a look at the latest phase 1 data in the KRAS niche.

What more clinical data already?!

Yes there is and what’s more it doesn’t belong to the either of the leading two in the early race to market, aka Amgen and Mirati.  There’s a whole bigger world out there for those interested in following the broader slate runners and riders.  It pays to pay attention because this is not a race about single agent therapies, rather it’s about who figures out the optimal combinations and is able to finesse that better than their competitors.  Like real horse races, an unexpected runner can surprise a few folks by making a strong push on the rails or a bounding leap round the outside like Lester Piggott was famous for doing.

This highly specialised field is moving much faster than the BRAFV600E arena was a decade ago and there’s also more players involved too, plus multiple different approaches and targets to consider, which I expect we will be covering quite a few times during 2020.

Are you ready?

Get set, GO!

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In Pharmaland it is frequently the case that once a target has been validated there’s always new developments in the form of novel agents that emerge, as well as emerging new related targets to consider.

Standing from the KRAS crowd

Here we combine an update on some new market entrants in the KRAS niche with an expert interview discussing how to address a known area of acquired resistance that has recently been highlighted.  Naturally, that also brings with it yet more novel targets and potential combination strategies that may need to be considered by players in this space.

Yes, KRAS G12C is now a rapidly evolving area with multiple players and many moving parts, whereas even just back in January this year many observers saw it as a three horse race – think again, it’s much deeper and broader than that somewhat naive hypothesis already!

As usual, we follow these races longitudinally with regular updates and explain why new scientific findings need to be considered if we are to make a difference in the clinic with future combination strategies.

Are you ready for the latest game of 3D chess?

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As we head into the AACR-NCI-EORTC Triple meeting in Boston this weekend, excitement is growing around a suite of RAS inhibitors in lung, colon and other cancers.

Charles River, Boston in October

Over the last couple of weeks we’ve received a bunch of questions from readers on several topics relating to this niche that I thought would be useful to spend some time on to set the scene ahead of the data dump expected on Monday and Tuesday.

Some people do like to try and simplify things thinking that it’s just a matter of adding in a checkpoint blocker or something else and boom! off we go… Except that we know from past experience with similar agents against different related targets that this won’t necessarily be the case and we look at some of the reasons why.

Yes I know folks are likely expecting too much in terms of efficacy, but we can put some framework and structure around the issues on which to build on, which are actually more than many may realise plus it could also be tumour and even patient dependent.

So here we go with a joint KRAS mailbag, together with a short expert interview with a view to highlighting some crucial roadblocks that are likely heading our way…

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